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CADUCEUS 



A Humanities Journal for Medicine 
and the Health-Sciences 




Historical and Contemporary Aspects of 
Communicable Disease Control 



SPRING 1996 ♦ VOLUME 12 ♦ NUMBER 1 



Digitized by the Internet Archive 

in 2011 with funding from 

CARLI: Consortium of Academic and Research Libraries in Illinois 



http://www.archive.org/details/caduceushuman1211996unse 



CADUCEUS 

A Humanities journal for Medicine and the Health Sciences 
Volume 12 ♦ Number 1 ♦ Spring 1996 



Contents 

2 Introduction: Historical and Contemporary 
Aspects of Communicable Disease Control 
Pascal James Imperato, Guest Editor 

7 An Epidemiologic Analysis of the Ten 
Plagues of Egypt 
John S. Marr and Curtis D. Malloy 

25 Cholera: Outlook for the Twenty-First Century 
John P. Craig 

43 The Tuberculosis Story: From Koch to 
the Year 2000 
Mahfouz H. Zaki and Mary E. Hibberd 

61 Smallpox and Measles in Mali: Contrasting 
Control Strategies and Outcomes 
Pascal James Imperato 



COVER: Block of 1969 stamps issued by the Republic of Mali in honor of the smallpox vaccination 
campaign. The stamps are provided by Pascal J. Imperato, whose article begins on page 61 of this issue. 

Copyright 1996 by the Board of Trustees of Southern Illinois University, ISSN No. 0882-7447 



Published by the Department oi 

Medical Humanities 
Southern Illinois University 
School ot Medicine 

Editors 

lohnS. Haller, |r„ IJitor 
Phillip V. Davis, Deputy Editor 
Mary Ellen McEUigott, 

Managing t ditoi 
Jean L. Kirchner, Editorial 

Researcher 

Department of Medical Humanities 
I heodore K 1 eBlang, Cluu 
M I vnne Cleverdon, 

Assistant to the Clmtr 
Barbara Mason, Curator, 

The Pearson Museum 
lean I . Kirchner, 

Subscription Manager 

Caduceus is produced for the 
Department of Medical 
Humanities by the Division oi 
Biomedical Communications, 
Southern Illinois University 
School of Medicine. 
Jim Hawker, Coordinator 
Linda Clark Ragel. Designer 
Patricia Baker, Typesetter 



An Introduction 



Historical and Contemporary 
Aspects of Communicable Disease 
Control 



Pascal James Imperato, Guest Editor 



There is a renewed interest in communi- 
cable diseases in the United States as 
we approach the close of the twentieth cen- 
tury. That interest may seem paradoxical 
since this is the century in which the major 
communicable diseases were believed con- 
quered in this country through a combina- 
tion of improved living standards, sanitary 
measures, vaccines, and antibiotics. So dra- 
matic was the decline in morbidity and mor- 
tality from such major communicable 
diseases as polio, measles, and rubella, that 
by the early 1970s the New York City De- 
partment of Health had difficulty recruiting 
a director for its Bureau of Communicable 
Disease Control. 1 Yet this was the bureau 
that only a few years before had investigated 
major epidemics made famous by Berton 
Roueche in his book Eleven Blue Men. 2 

There were several reasons why commu- 
nicable disease control had fallen to a lower 
priority in public health. Dramatic reduc- 
tions in the morbidity and mortality of those 
diseases generated excessive confidence in 
the abilities of vaccines and antibiotics alone 
to control them. Other public health priori- 



ties — including lead poisoning and the her- 
oin epidemic — moved to center stage and 
received significant levels of both federal 
and state funding. There was a failure to 
recognize that changing demographic pat- 
terns due to immigration from disease-en- 
demic Third World countries would soon 
introduce large numbers of infected indi- 
viduals, as in the case of tuberculosis. Re- 
grettably, public policy makers and 
legislators cut funding for immunization 
programs, failing to realize that inadequate 
access to them for poor inner-city and rural 
children would create large pools of suscep- 
tibles capable of sustaining new epidemics 
and outbreaks. Finally, there was little un- 
derstanding that social behaviors could start 
and sustain epidemics. The role of crack co- 
caine in generating the national syphilis epi- 
demic of the late 1980s and early 1990s is a 
recent example of the powerful influence of 
a social determinant on disease morbidity. 3 
For most of the 1970s, public health de- 
partments in the United States provided 
steady but back-burner support for commu- 
nicable disease control activities. The 1976 



CADUEUS ♦ Spring 1996 ♦ Vol. 12, No. 1 



outbreak of Legionnaires' disease in Phila- 
delphia caused some public health leaders to 
rethink their spending priorities. Most, how- 
ever, viewed the Philadelphia and sub- 
sequent outbreaks of the disease as unusual 
events that did not require a shift in resource 
allocation. That complacency was reinforced 
when the predicted 1976 Swine Flu epidemic 
did not occur. 4 Yet from a certain perspec- 
tive, the outbreaks of Legionnaires' disease 
of the 1970s and cases of toxic shock syn- 
drome in the early 1980s put public health 
departments on alert to the reality that they 
could no longer take communicable disease 
control for granted. Despite the disappear- 
ance of naturally transmitted smallpox in 
1977 and the development of more effective 
vaccines and antibiotics, prescient public 
health specialists and scientists recognized 
that newer pathogens might emerge from 
man's manipulation of his environment, and 
that existing pathogens could soon prove to 
be resistant to known prophylactic and 
therapeutic agents. 

By the mid-1980s, after a lapse of almost 
two decades, communicable disease control 
units were once again at the center of public 
health departments. This dramatic shift was 
brought about by the epidemic of acquired 
immunodeficiency syndrome (AIDS) in the 
early 1980s. As federal and state funding 
improved, public health departments re- 
built their communicable disease control ca- 
pabilities around AIDS. Infections such as 
tuberculosis and syphilis, which reappeared 
in epidemic form in the late 1980s, sustained 
their strong commitment to communicable 
disease control. Finally, emerging patho- 
gens, notably the Ebola virus, have demon- 
strated that the future of communicable 
disease control contains many unknowns. 

The emerging pathogens of the 1990s have 
caused a drastic change in how we now view 



REPUBUOUE DU MALI 
POSTES E7 TELECOMMUNICATIONS 





CAMPAGNE COMTPE LA VARIOLE ET LA WUCEOLE 



PREMIER JOUR D EMISSION 



Tinge llmlte (numerate de 1 a 20031 (^0 1 3 8 5 



This first-day cover for a 50 franc stamp, issued November 10, 1969, 
commemorated the smallpox eradication/measles control program in Mali. 



communicable disease control. The exces- 
sive confidence of the 1970s has given way 
to a greater realization of the complexities of 
human/pathogen interactions. There has 
also been a commitment of resources. That 
understanding and commitment are fueled 
not only by the insights of scientists but also 
by the concerns of the American public, who 
have learned that these pathogens are often 
fatal, defying easy solution through the use 
of vaccines and drugs. They both fascinate 
and frighten, and often appear because we 
alter and disrupt the delicate balances be- 
tween them, us, and the environment we 
share. 5 

World population growth has given rise 
to human encroachment on what were once 
the wild refuges of many pathogens. In those 
remote forested environments, viruses such 
as Ebola have reached a state of equilibrium 
with natural hosts over many millennia. 
Once transported from that balanced envi- 
ronment, the viruses cause lethal epidemics 
as they enter a human population with 
which they have had little or no contact. 

Man is not only coming into contact with 
new viruses but also transporting old ones 



Pascal James Imperato 3 



I 1 



The Ped-O-Jet 
automatic jet 
injector being used 
to administer 
measles vaccine, 
San, Mali, 1968 




to different locations. We facilitate the 
spread of epidemics by manipulating our 
indoor environments and the food we eat. 
Our excessive and often unnecessary use of 
antibiotics has given rise to resistant strains 
of bacteria. The result has been dramatic 
rises in deaths from pneumonia and septice- 
mia, often among hospitalized elderly pa- 
tients. In response to the growing threat of 
infectious diseases, the Journal of the Ameri- 
can Medical Association and thirty-five other 
medical journals joined together on January 
16, 1996, in a concerted call for increased 
efforts against these diseases. 6 The editors 
simultaneously published a total of 242 arti- 
cles on the subject to emphasize its impor- 
tance. One of the most sobering statistics to 
emerge from those studies is that, exclusive 
of AIDS, infectious disease mortality rose by 
22 percent in the United States between 1980 
and 1992. 7 

If the first eight decades of the twentieth 
century were marked by continued success 
in the control of communicable diseases, the 
last two decades have brought us to the so- 
bering frontier of emerging and reemerging 
infections. We now recognize that we will 
have to deal continuously with newer epi- 
demics due to our disruption of the environ- 
ment, as well as with older ones that emerge 
because of social, technical, and behavioral 
determinants. 



The essays in this issue of Caduceus dem- 
onstrate both the complexities of several 
pathogens and the challenges inherent in 
attempts to control the epidemics they 
cause. In addition, John S. Marr and Curtis 
D. Malloy present a new and interesting uni- 
tarian hypothesis concerning the ten plagues 
of ancient Egypt. They use a modern 
epidemiologic approach to analyze these 
plagues, discuss previous scholarly conclu- 
sions, and use the entire corpus of available 
data to formulate their new hypothesis. 
Their conclusions will certainly not be the 
last on this approximately 3,500-year-old 
story. They will however, stimulate further 
reflection and discussion, proving once 
again the wisdom of the ancient Greeks, who 
observed: "There is always something new 
out of Africa." 8 

John P. Craig discusses the fascinating 
story of the Seventh Cholera Pandemic, 
which began in 1961. His essay presents in- 
triguing details about the epidemiology, 
bacteriology, and immunology of the Vibrio 
cholerae. He shows how recent advances in 
oral and intravenous fluid and electrolyte 
replacement therapy, as well as greater ex- 
pertise on the part of medical personnel, 
have reduced mortality to less than one per- 
cent. This is a remarkable twentieth-century 
accomplishment for a disease that was once 
invariably fatal for half of those who con- 
tracted it. Yet, as Dr. Craig notes, cholera is 
primarily controlled today not by vaccina- 
tion or by breaking the chain of transmission 
but by treating people after they have con- 
tracted it. 

Tuberculosis, once known as the "white 
plague," was a major cause of morbidity and 
mortality in the United States in the early 
part of this century. 9 It caused enormous 
social disruption and great economic hard- 
ships as families were broken up in the inter- 



4 Historical and Contemporary Aspects 



ests of isolating victims in sanitoria. Isola- 
tion, rest, fresh air, and surgical procedures 
were all that medicine had to offer in terms 
of treatment. A vast system of state-operated 
sanitoria filled with tuberculosis patients 
was in existence until the 1940s, when anti- 
tuberculosis drugs became widely available. 
Most of these specialized hospitals were 
closed by the 1960s and 1970s, vivid testi- 
mony to the assumed conquest of yet an- 
other communicable disease. 10 Yet was the 
disease really controlled? As Mahfouz H. 
Zaki and Mary E. Hibberd describe in their 
essay on tuberculosis, early assumptions 
about eradication were quickly proven 
wrong. As disease prevalence declined in 
this country, however, federal funding for 
tuberculosis control programs was dramati- 
cally reduced. Such programs were given an 
increasingly lower priority in local health 
departments, based on the assumption that 
the disease was well under control. During 
the 1980s, the incidence of tuberculosis sud- 
denly surged in the United States due to 
imported infections among recent immi- 
grants and AIDS-associated disease. 

As Drs. Zaki and Hibberd describe, there 
are many newer and difficult challenges 
posed by this reemerged infection. Among 
them are multiple drug-resistant strains and 
the growth of patient noncompliance with 
drug treatment. Zaki and Hibberd detail the 
enormous financial costs of controlling the 
resurgent tuberculosis epidemic. They also 
make the cogent observation that relaxing 
control measures and reducing funding for 
a disease whose incidence is declining is a 
serious public health policy error. 

The fourth essay in this issue contrasts the 
control strategies and outcomes for small- 
pox and measles in the West African country 
of Mali. A focused country study, it serves to 
illustrate a number of the issues and prob- 



lems that confronted many of the other 
eighteen West and Central African countries 
that participated in a multiyear effort to 
eradicate smallpox and control measles. 

The eradication of smallpox stands as one 
the great public health achievements of the 
twentieth century. The success of the eradi- 
cation effort in West and Central Africa was 
in large measure due to the dedication and 
expertise of American personnel assigned to 
individual countries. Backed by a commit- 
ted leadership staff at the Centers for Disease 
Control in Atlanta, these young physicians 
and operations officers left for Africa full of 
enthusiasm, hope, and even trepidation. 
Their determination had been galvanized 
over a period of several months in Atlanta, 
where they were trained not only to diag- 
nose smallpox and investigate epidemics 
but also to speak French and repair the en- 
gines of Dodge trucks. 

The field staff of courageous young 
Americans was fortunate in having an expe- 
rienced and accomplished physician as their 
leader. George Ignatius Lvthcott never wa- 
vered in his belief that smallpox could be 
eradicated. As regional director for the West 
and Central African Smallpox Eradica- 
tion/Measles Control Program, he continu- 
ously pursued that goal. More important, he 
provided his staff with the encouragement, 
support, and counsel needed to overcome 
enormous odds. In so doing, he helped cre- 
ate the ultimate triumph of eradicating a 
disease. 11 

The closing vears of the twentieth century 
are a fitting time to examine different aspects 
of communicable disease control. For this is 
the century in which historic advances took 
place in the prevention, control, and treat- 
ment of man\ - diseases. Antibiotics were de- 
veloped and have saved millions of lives. 
Effective vaccines for preventing the killer 



Pascal James Imperato 5 



lives. Effective vaccines for preventing the 
killer diseases of childhood have allowed 
youngsters all over the world to reach adult- 
hood. Improved living standards and sani- 
tation have helped to interrupt disease 
transmission, and science has found the 
means to treat even viruses. 

This is also the century, however, in which 
we came to realize that combinations of so- 
cial, technical, and behavioral determinants 
greatly influence the life histories of commu- 
nicable diseases. Emerging and reemerging 
epidemics — as well as antibiotic resis- 
tance — have their origins in human actions. 
Both scientists and the public now know that 
future successes against these diseases will 
not be achieved through a reliance on drugs 
and vaccines alone. The essays in this issue 
of Caditcens address some of these issues, 
and bring the lessons of history to bear upon 
present and future efforts at communicable 
disease control. 



Notes 



1. Pascal James Imperato, Medical Detective 
(New York: Richard Marek Publishers, 1979), 163- 
64. 

2. Berton Roueche, Elei'en Blue Men and Other 
Narratives of Medical Detection (Boston: Little Brown 
& Co., 1953). 

3. R. T. Rolfs and G. P. Schmid, "The United 
States syphilis epidemic: Reason for optimism (at 
least for the moment)," New York State journal of 
Medicirie 91 (1991): 522-23. 

4. Richard E. Neustadt and Harvey V. Fineberg, 
The Swine Flu Affair. Decision-Making on a Slippery 
Disease (Washington, D.C.: U.S. Department of 
Health, Education, and Welfare, 1978). 

5. Emerging pathogens currently attract much 
popular attention. They have been the subject of 
popular books (e.g., Laurie Garrett, The Coming 
Plague: Newly Emerging Diseases in a World out of 
Balance [New York: Farrar, Straus and Giroux, 



1994]), a Hollywood film ("Outbreak"), front-page 
news stories, and prime-time television coverage. 

6. D. A. Goldmann, R. A. Weinstein, R. P. Wen- 
zel, et al., "Consensus Statement: Strategies to Pre- 
vent and Control the Emergence and Spread of 
Antimicrobial-resistant Micro-organisms in Hospi- 
tals: A Challenge to Hospital Leadership," JAMA 
275 (1996): 234-40; J. A. Patz, P. R. Epstein, T. A. 
Burke, et al. "Global Climate Change and Emerging 
Infectious Diseases," JAMA 275 (1996): 217-23; J. 
Lederberg, "Infection Emergent," JAMA 275 (1996): 
243-45; M A. Winker and A. Flanagin, "Infectious 
Diseases: A Global Approach to a Global Problem," 
JAMA 275 (1996): 245-46. 

7. "Doctors Tell of International Resurgence in 
a Variety of Infectious Diseases," Neiv York Times, 
Jan. 17, 1966, A16; R. W. Pinner, S. M. Teutsch, L. 
Simonsen, et al., "Trends in Infectious Diseases Mor- 
tality in the United States," JAMA 275 (1996): 189-93. 

8. Pliny the Elder (23-79), a Roman scholar, 
popularized the Greek proverb in Latin as "Ex Af- 
rica semper aliquid novi." 

9. R. J. Dubos, "Biologic and Epidemiological 
Aspects of Tuberculosis," American Revieiv of Tuber- 
culosis 68 (1953): 1-8. 

10. K. W. Wright, J. Monroe, and F. Beck, "A 
History of the Ray Brook State Tuberculosis Hospi- 
tal," New York State Journal of Medicine 90 (1990): 
406-13. 

11. Lythcott later became associate dean for ur- 
ban and community affairs at the Columbia 
University College of Physicians and Surgeons, as- 
sociate vice-chancellor for academic affairs at the 
University of Wisconsin, and in 1977 was appointed 
by President Jimmy Carter as administrator of the 
health services administration in the Department of 
Health and Human Services. He then served as dean 
of the City University of New York's Sophie Davis 
School of Biomedical Education, and later as assis- 
tant commissioner in the New York City Depart- 
ment of Health. He died at his home on Martha's 
Vineyard on Oct. 7, 1995. See Wolfgang Saxon, 
"George Lythcott, 77, Pediatrician, Dean and Health 
Official," New York Times, Oct. 11, 1995, B8. 



ACKNOWLEDGMENTS 

Thanks are extended to Florence Kavaler, M.D., for her 
helpful suggestions and to Lois Hahn for her careful 
preparation of the typescript. 



6 Historical and Contemporary Aspects 



An Epidemiologic Analysis of the 
Ten Plagues of Egypt 



John S. Marr and Curtis D. Malloy 



The Ten Plagues of Egypt described in 
the Book of Exodus are the first exam- 
ple in a historical written record of what 
today might be described as "emerging in- 
fections." Causes and interpretations of the 
Ten Plagues have fascinated theologians, 
historians, Egyptologists, musical compos- 
ers, scientists, and physicians for centuries. 
More recently other health professionals in 
various disciplines — including epidemiol- 
ogy, epizootiology, entomology, microbiol- 
ogy, and toxicology — have postulated 
probable causes for one or more of the 
plagues. In recent years reinterpretations of 
ancient texts and new information about en- 
vironmental factors and disease causation 
have allowed unique interpretations of that 
series of early public health catastrophes. 
Yet despite centuries of study, fundamental 
questions remain. 

Were the Ten Plagues historical events, or 
perhaps only a collection of religious arche- 
typal stories or myths? If the plagues did 
occur, why were there no specific citations 
to them in ancient Egyptian literature? If 
Egyptological research suggests some sem- 
blance of their occurrence, who might best 
"fit" as the candidate for pharaoh presiding 
over the plagues' occurrence? If a specific 
pharaoh can be posited (and satisfactorily 
reconciled within the more accepted talmu- 
dic and biblical chronological timeframes), 



when and where in time and place (theologi- 
cal and Egyptological) would the plagues 
under his reign and the ensuing Exodus 
have occurred? After those questions have 
been addressed, one is in a better position to 
offer a scientific interpretation to these ques- 
tions: What were the causes of each of the 
Ten Plagues? How did they occur? 

This paper will attempt to integrate biblical, 
historical, and Egyptological data to support a 
logical conjecture for the specific time, place, 
and pharaoh. Our conclusions follow the tra- 
ditional tenets of epidemiologic investigation, 
the first of which is to answer the question, 
"Was there an epidemic?" That will be fol- 
lowed by corollary questions of when, where, 
and who might have been affected — the time- 
place-person questions of descriptive 
epidemiology. We then address specific ex- 
planations for each of the Ten Plagues, at- 
tempting to answer the "how" and "why" of 
analytical epidemiology. 

Previous authors have postulated many 
explanations of the plagues — theological, 
supernatural, quasi-scientific, and scientific. 
We will address those extensive and good 
works, using Occam's razor as needed to 
reduce discordant explanations to the sim- 
plest and most logical. We then propose that 
the first nine plagues built upon each of the 
preceding plagues, and precipitated the final, 
most devastating plague, which culminated 



CADUCEUS ♦ Spring 19% ♦ Vol. 12, No. 1 



in finally having the pharaoh agree to 
Moses' demand to "let my people go" (Exo- 
dus 5:1). 2 

Did the Ten Plagues Occur? 

The epidemiologic analogue to the above 
question is "Was there an epidemic?" If the 
answer is no, the investigation is terminated. 
There is some evidence, however, separate 
from the original talmudic and biblical ac- 
counts, that the plagues did occur. Im- 
manuel Velikovsky has cited passages from 
the Admonitions of Ipuzver (as translated in 
1909 by Sir Alan H. Gardner), an ancient 
Egyptian papyrus, which substantiates that 
a series of catastrophes did occur at the end 
of the Middle Kingdom. 3 One of the earliest 
and most complete analysis of possible 
causes of the plagues was offered by Greta 
Hort, who based her theory on passages 
from the papyrus. 4 

Who, Where, and When? 

There is little if any secular information to 
substantiate the historicity of the Exodus 
account. Some Egyptologists consider the 
Bible as story, not as history, noting that half 
a millennium or more had passed between 
the time of those events and the time of the 
first known written Hebrew literature. A 
strictly historical analysis would reveal that 
if the plagues and the Exodus did occur, they 
must have transpired before 1200 B.C.E., 
when the so-called "Israel" stela of the Phar- 
aoh Merneptah described a people — not a 
country — called "Israel" that had already 
reached Canaan. 

Furthermore, some have criticized utiliz- 
ing the Ipuwer papyrus to substantiate the 
Exodus account, stating Ipuwer simply pro- 
vides a contrast to the transition from a pre- 



viously chaotic environment to the sub- 
sequent reign of a just and capable ruler. 

Many scholars who believe that the 
plagues actually occurred nevertheless dis- 
agree on the identity of the reigning pharaoh 
(and therefore on the likely years). Hort 
wisely ignores the question. Donovan A. 
Courville, after considerable debate, was 
unable to make a determination. Citing first 
century AD. Jewish theologian Josephus as 
an authority, Cecil B. DeMille chose Ra- 
messes II for his cinematic rendition TJie Ten 
Commandments. In 1981 Biblical scholar 
Werner Keller also reasoned that Ramesses 
II was the pharaoh. H. M. D. Hoyte, on the 
other hand, citing John J. Bimson, concluded 
in 1993 that the pharaoh was Thutmose III. 
Velikovsky appears to concur with Hort, 
although his candidate is not specified. He 
identifies a "Taui Thorn the last king of the 
Middle Kingdom. He is the Tau Timaeus 
(Tutimaeus of Manetho)." Egyptologists to- 
day prefer the spelling of Thutmose for the 
various New Kingdom, 18th Dynasty rulers. 
Independent of various spellings, however, 
all four Thutmoses (I-IV) reigned well after 
the Hyksos, who were posited by Veli- 
kovsky. 5 

A definitive identification of the pharaoh 
is of some interest since the two (or more) 
postulated pharaohs span different time pe- 
riods, varying slightly, depending on the 
source of dating: Ramesses II (1290-1224 
B.C.E.); Thutmose I (1504-1492 B.C.E.); Thut- 
mose II (1492-1479 B.C.E.); Thutmose III 
(1479-1425 B.C.E.); and Thutmose IV (1401- 
1391 B.C.E.). For Velikovsky that is of greater 
importance, as he ties the plagues and fiery 
pillar and parting of the Red Sea to other 
contemporary Old and New World histori- 
cal accounts. His overall explanation is a 



8 Ten Plagues of Egypt 



series of major climatological disasters pre- 
cipitated by a comet and coinciding with the 
Hyksos invasion. Unfortunately, the Hyk- 
sos period (1640-1532 B.C.E.) does not coin- 
cide with any of the four Thutmoses. 6 

Hoyte suggested that the Ten Plagues 
took place under Thutmose III (1479-1425 
B.C.E.) over an eleven-month span, begin- 
ning in July-August and lasting through 
April-May of the following year. Neither 
the two pharaohs suggested by most schol- 
ars — Thutmose III or Ramesses II — nor the 
duration of ten months within which those 
plagues may have taken place, are incom- 
patible with the selected notations of the 
Ipuwer papyrus. 

Scholars do agree that the ancient city of 
Memphis (today, Mit Rahina), located at the 
mouth of the Nile delta, was the residence of 
late Middle Kingdom and early New King- 
dom pharaohs. A consensus supports that 
the land of Goshen was somewhere north- 
east of Memphis, near the ancient (now lost) 
city of Heliopolis, a few miles north of pre- 
sent-day Cairo. Heliopolis was referred to in 
the Bible as "On, Aven, and Beth-Shemesh." 
Hort proposed that Goshen lay some fifty 
miles northeast of Heliopolis, in the Wadi 
Tumilat near present-day Tell el-Maskhuta, 
a river valley that once connected the Nile to 
the northern extension of the Red Sea. If 
Goshen existed today, it would be about 
fifty miles northeast of present-day Cairo, 
less than one hundred miles from what is 
today known as the Gaza strip. The Red Sea 
is viewed by most historians as a mistrans- 
lation of the reed sea, a marshy extension of 
water extending from the Red Sea toward 
southwest Gaza. Indeed, a fast, primarily 
easterly exit from Memphis (29.8"), through 
Heliopolis (30.1°) and Goshen (Wadi Tumi- 
lat, 30.8") would be well above the north- 
ernmost extension of the Red Sea (30. 0'). 7 




Interpretations of the Ten Plagues of Egypt 

Interpretations of what the Ten Plagues 
might have been can be grouped into two 
categories: theological and scientific. The 
former group explores not only alternative 
translations of the original Hebrew and Ara- 
maic texts but also secondary biblical inter- 
pretations. Scientific writers offer 
explanations for either a specific plague, a 
selected subset of plagues, or all ten of them. 
They further propose either separate expla- 
nations for each plague or procrustean theo- 
ries to identify a single common factor or 
condition. We have chosen to discuss the 
plagues in pairings of successive twos, 
which we believe is the simplest way of 
discussing and building toward a logical 
and unified conclusion for the final, devas- 
tating plague. 8 For a summary of all inter- 
pretations, see pages 12-13. 

First and Second Plagues— Fresh Waters Turn to 
Blood and Frogs 

Prior to the germ theory, the only expla- 
nation posited for the cause of the first 
plague was an unknown noncontagionist 



Seal of Thutmose III 

(Reproduced with 
permission from 
John Barnes and 
Jaromir Malek, 
Atlas of Ancient 
Egypt [New York: 
Facts on File, 19891) 



John S. Marr and Curtis D. Malloy 9 



theory of "contamination" that could cause 
an extensive fish kill. After the advent of the 
germ theory, more specific infectious and 
noninfectious causes have been postulated. 
Silt remained an early candidate as the cause 
of a reddish Nile; later, that explanation was 
refined to a specific silt known as "marl," 
originating from Ethiopia and carried by a 
cresting Blue Nile. Velikovsky's more recent 
proposal was that cometary red dust caused 
the Nile to turn color. 9 

Recent explanations for the red-colored 
waters have favored protozoan, zooplank- 
ton, dinoflagellates, and both salt- and fresh- 
water algal (phytoplankton) blooms. All of 
those blooms — plant, fungal, or proto- 
zoan — deoxygenate water and produce 
noxious toxins for both fish and frogs. With- 
out predator fish, frogs could initially breed 
freely in both ponds and the Nile; in time 
they would overpopulate the river, eventu- 
ally escaping the anoxic, toxic, and putrefy- 
ing environment by migrating to land, hence 
to die and decompose along with the fish. 
The Nile and adjacent land would thus be- 
come fouled, and the waters dangerous to 
drink or bathe in. 

P. A. Tester, citing the Exodus account, 
noted that while fewer than fifty out of ap- 
proximately five thousand known phyto- 
plankton species are toxic, those that possess 
toxins can be dangerous to aquatic life. E. C. 
D. Todd, referring to historic and prehistoric 
data, cites nearly two dozen examples of 
specific phytoplanktons causing various 
outbreaks throughout the world. Wayne W. 
Carmichael listed diseases associated with 
freshwater blue-green algae. JoAnn M. 
Burkholder described the dinoflagellate Pfi- 
esterin piscimorte, which was found in estuary 
waters and, as the species name implies, was 
capable of killing fish. Neither an unstated 
contamination, cometary dust, nor silt 



would by itself explain all of the phenomena 
described above. In addition, the Nile, its 
tributary waters, well water, and other bod- 
ies of standing water were fresh. Most of the 
above-mentioned aquatic, phytotoxic 
blooms occur in salt or brackish water, with 
the exception of the recent discovery of 
freshwater blooms. 10 

We conclude that a freshwater dinoflagel- 
late biomass bloom, as described by Car- 
michael and Burkholder, was responsible 
for the change in the color of the Nile, the 
death of fish, and the subsequent population 
explosion among frogs. 

The death of fish — "an important source 
of protein and minerals" for the ancient 
Egyptian, was more than an inconvenience. 
It was the first of many nutritional compro- 
mises caused by ensuing plagues to be in- 
flicted on the Egyptian Empire, culminating 
in the last plague. The eventual death of 
frogs also removed an important health 
agent, for frogs were the natural enemy of 
certain biting insects that were otherwise 
free to multiply unhindered. 11 

Third and Fourth Plagues— Lice and the Swarm 
of Flies 

The first mention of two of the three mem- 
bers of the Class Insecta (Hexapoda) is of 
particular interest to entomologists (the sec- 
ond mention occurs with the locusts of the 
seventh plague). Richard L. Brown has 
noted that any identification of an insect by 
either order or genus in the Book of Exodus 
predates the first taxonomic attempts by 
Aristotle to classify insects (or arthropods) 
by nearly one thousand years. Thus, any 
arthropod may be considered a putative 
vector, including the members of the Class 
Arachnida — soft ticks, hard ticks, scorpions, 
spiders, and mites. All such arthropods 
abounded in Egypt. 12 



10 Ten Plagues of Egypt 



The original Hebraic term for "lice" is 
most often translated as "vermin." That 
term, as such, is commonly construed as an 
arthropod skin infestation, not as flying in- 
sects. The term also implies that the multiple 
offenders could be visibly recognized. Thus, 
the otherwise ingenious conclusion by J. 
Korzets that the cause of the third plague 
"itch" was due to the microscopic scabies 
mite (Sarcoptes scabiei) is probably incorrect, 
although David J. Sencer notes that the 
chronic allergic sequela of that infestation, 
"beggars' itch," is an alternative explana- 
tion. Of the three human body lice known 
today (Pediculus corporis humanis, P. capitis 
humanis, and Pthirus pubis), none fulfill the 
description of the macroscopic infestation 
"on man and beast," since those lousy can- 
didates are species-specific, and do not in- 
fest nonhuman hosts, as the text clearly 
states. 13 

Alternative explanations are such indis- 
criminate biters as the soft tick (Orthinodoris 
moubati), hard tick (Boophilus annulatus), and 
maggot infestation or myiasis (e.g., Dermato- 
bia hominis) found in North Africa. Although 
entomologically correct for Egypt, all of 
those dermatological infestations are too 
macroscopic to warrant usage of the term 
"vermin." And, like lice, none have the ca- 
pability of flying. 

Of flying insects resident in Egypt, recent 
findings that Simulian species of blackflies 
transmitting onchocerciasis (river blind- 
ness) in many areas of eastern Africa (includ- 
ing the Sudan) offers another explanation. The 
dermatosis caused by those flies is singularly 
characterized by intense itching. Even if 
blackflies were candidates for the "lice," 
however, the vector is too large and recog- 
nizable to be called vermin, and the pruritus 
induced by an allergic reaction to the death 



of O. volvulus microfilaria takes months or 
years to appear. 

Hoyte suggests an alternative to the He- 
braic translation of "chinnim" — the Greek 
"sciniphes," or -mosquito/gnat. More than 
forty species of mosquito capable of trans- 
mitting disease have been cataloged in 
Egypt; the most abundant genera of mos- 
quito, in decreasing order, are Anopheles, 
Culex, Aedes, Culiseta, and Uranotaenia. Mos- 
quitoes are relatively large and easily recog- 
nized. Nevertheless, Hoyte preferred the 
mosquito Culex antennatus as the most likely 
explanation for "lice." By so doing, he dis- 
missed the midge and sandfly as both the 
cause of the infestation and as a possible 
vector for subsequent plagues. 14 

The midge, a lay term that includes Culi- 
coides species (also known as gnats, "no-see- 
ums" and "punkies") are nematocerous flies 
whose larvae and pupae live in moist soil. 
They are small and bloodsucking, thus bet- 
ter fulfilling the near-microscopic descrip- 
tion of "lice"; furthermore, they may appear 
to originate in "dust" because their pupae 
develop and eventually fly out from what 
would appear as dirt or dust. The same is true 
for sand flies (Phlebotomus species). Eight 
species of Culicoides and seven species of 
Phlebotomus have recently been identified in 
Egvpt. The latter is a vector of sandfly fever 
and leishmaniasis (visceral and cutaneous). 
Those two zoonoses are unlikely to be con- 
fused with either the fifth or sixth plagues. 15 

Unlike the sand fly, which lays it eggs in 
cracks in walls or stone outcroppings, Culi- 
coides larvae feed on abundant microorgan- 
isms in decomposing detritus, such as the 
remains of fish and frogs. The eventual ex- 
plosive emergence of adult flies might be 
well construed as a plague coming from "all 
the dust of the land." 



John S. Marr and Curtis D. Malloy 11 



Summary of Interpretations Given to the Ten Plagues of Egypt 



Plague 

ARAMAIC 
HEBREW 



Biblical Passage 



Chapter, Verse 



Ipuwer Papyrus 



Interpretation 



Bryant 

England/1810 

Blanc 

United States/1890 

Velikovsky 

USSR/1950 

Hort 

Netherlands/1957 

Schoental 

United States/1980 

Schmidt 

Germany/1990 

Jacoby 

United States/1990 

Hoyte 

Australia/1993 

Ceccarelli 

Italy/1 994 

Marr, Malloy 
United States/1996 



1. Water to Blood 2. Swarm of Frogs 3. Plague of Lice 4. Swarms of Flies 

DAM TSTAR-DEI-A KI-NIM A-ROV 

B«r srnas o'» any 



"Stretch out thine hand upon 
the waters of Egypt: upon 
their streams, upon their riv- 
ers, upon their ponds, upon 
their pools of water, that they 
may become blood." 



Exodus 7:19 

"Lo, the river is blood, As 
one drinks of it one shrinks 
from the people. And thirsts 
tor water." 



"tainted and 
polluted streams" 



"Stretch forth thine hand with 
thy rod over the streams, 
over the nvers, and over the 
ponds, and cause frogs to 
come up upon the land of 
Egypt." 



Exodus 8:5 



"Aaron stretched out his 
hand with his rod, and smote 
the dust of the earth, and it 
became lice in man, and in 
the beast; all the dust of the 
land became lice, through 
the land of Egypt." 



Exodus 8:16 



"fnhere came a gnevous 
swarm of flies intothe house 
of the Pharaoh, and into his 
servants' houses, and into 
all of the land of Egypt; the 
land was corrupted by 
reason of the swarm of flies." 



Exodus 8:24 



"Towns are ravaged, Upper 
Egypt became wasteland. 
Lo, crocodiles gorge on their 
catch.'f 



Frogs (a diety) and their 
death are emblematic of a 
prophetic influence 

Anthrax 

(Bacillus anthracis), 

infected and killed frogs. 



Lice: "vermin . . . pediculi" 



(House?) flies 
representing "Zebub" 



Flies transmitting anthrax Flies transmitting anthrax 



The fall of red meteorite 

dust from a comet polluting 

waters 

Red silt, flagellated protozoa 

Euglena sanguina, 
Haematococcus pluvialis 

Microfungi and 

Fusanum roseum 

contaminating waters 

Waters contaminated 
by dead fish 

Nile (a diety) waters made 

undnnkable 

secondary to dead fish 

Dinoflagellates 

Gymnodtuium and Glenodintum 

(unnamed species) 

Dinoflagellates 

Gymnodiuium and Glenodinium 
species (after Hoyte) 

Freshwater cyanobacteria 

causing river to turn red, 

and killing fish 



Anthrax 

(Bacillus anthracis), 

infected and killed frogs. 

Frogs killed by 

dinoflagellates producing 

soluble poisons 



Frogs 



MosquitOS 
(Culex species) 



"vermin" 



Frogs 



Dehydration and 

desiccation killed escaping 

frogs 



Frogs 

Frogs leave deoxygen- 

ated waters and die, 
contributing to Plague 3 



"Sand fleas," not gnats 



"Midges" 
(Culex antennatus) 

"Midges" 

Culex antennatus 

(after Hoyte) 

CuScoides appear de novo from 

pupae hatching in sand (Hoyte) 

transmitting Plague 5 



Stable flies 

(Stomoxys calcitrans) 

transmitting Plagues 5 & 6 



Horseflies 



"An insect akin to a winged 
ant" 

Stable flies 

Stomoxys calcitrans 

(see Hort) 

Streptococcal and 

Staphylococcal infections; 

Babesiosis 

Stable flies 

(Hort and Hoyte) 

transmitting Plague 6 



f Some rabbinical scholars have interpreted the Hebraic text as possibly meaning amphibians in general. 



12 Ten Plagues of Egypt 



5. Animal Murrain 6. Boils and Blains 
DE-VER SH'HIN 

nan *"rw 



"Behold the hand ol the Lord 
is upon thy cattle which is in 
the field, upon the horses, 
upon the asses, upon the 
camels, upon the oxen, and 
upon the sheep; there will 
be a gnevous murrain." 



Exodus 9:3 

to, all beasts, their heads 
shall weep. Cattle bemoan 
the state of the land." 



"the distemper" 



Anthrax 



Secondary skin 

infections from comet 

dusts 



Anthrax 



Mycotoxms 



Surra (debab) 
( Trypanasoma evansi) 



Babesiosis 
(Babesia bigemini) 

African horse sickness; 
Bfuetongue; Epizootic 
hemorrhaghic disease 



Take to you handf uls of ashes 
ot the furnace, and let Moses 
sprinkle it toward the heaven 
in the sight of fhe Pharaoh. 
And it shall become small dust 
in all the land of Egypt, and 
shall be a boil breaking forth 
with blams upon man. and upon 
beast, throughout all the land 
of Egypt." 

Exodus 9:8 



"Plague is throughout the 
land. Blood is everywhere." 



Thai where any atom ol this dust 
be whiffed might be entailed, but 
with a different intention . a 
plague and a curse." 

Anthrax 



Boils secondary to 

dusts, blisters from flaming 

naptha 



Anthrax 



2° bacterial infect, due to 

immunosuppression by 

tnchothecenes 



"herpes-like infection"'' 

"bubonic infection*? 

"Intlamation of sexual organs" 7 

Ecthyma 

(Group A hemoloytic 

Streptococcus pyogenes) 

Babesiosis 
(Babesia bigemini) 



Glanders (fancy) 
Pseudomonas mallei 



7. Hailstorms 

BA-RAD 
TO 



"Stretch forth thine hand to- 
ward heaven, that there will 
be hail in all the land of Egypt, 
upon man and upon beast, 
and upon every herb of the 
field, throughout the land of 
Egypt. " 



Exodus 9:22 

"Lo, hearts are violent, 
storms sweep the land." 



"thunder, hail, fire" 
destroy crops 



Hail 



Dust, gravel, and 
burning naptha 
from a comet 

Hailstorms destroyed 
flax and bartey but 
not wheat or spelt 



Hail 



Hail 



8. Locusts 

AR-BEH 

nans 



"[W]hen it was morning, the 
east wind brought the lo- 
custs. And the locusts went 
up over all the lands of Egypt, 
and rested in all the coasts 
of Egypt: very gnevous were 
they; before them there were 
no such they, neither after 
them shall be such." 



Exodus 10:13 

"Birds find neither fruit nor 
herbs. . . .Trees are de- 
stroyed. No fruit nor hems 
are found." 



Locusts caused famines 



Locusts 



Locusts 



Crops ruined by hailstorms 



Hail 



Halt destroying 

established crops and 

dampening stored foods 



Locusts ruined crops 



9. Darkness 

HOSHEKH 



"Moses stretched forth his 
hand toward heaven; and 
there was a thick darkness 
in all the land of Egypt three 
days: They saw not one an- 
other, neither rose from any 
of his place tor three days 
but all the Children of Israel 
had light in their dwellings " 



Exodus 10:22 

"Lo, the desert claims the 
land. . . . Those who had 
shelter are in the dark of the 
storm. . . Egypt will not be 
given over (to] sand.. . . The 
land is not light." 



"a preternatural state of 
night" 



Locusts swarms 



Cinder dust from 
a comet 



Sandstorms (khamsin) 



Darkness 9 



Sandstorms 



10. Death of Eldest 
MA-KAT B'KHO-ROT 

nmsa nsa 



"About midnight I will go out 
into the midst of Egypt: And 
all the first-bom in the land 
of Egypt shall die, from the 
firstborn of Pharaoh that 
sitteth upon his throne, even 
unto the firstborn of the maid- 
servant that is nehmd the 
mill; and all the firstborn of 
the beasts ' 



Exodus 11:4 

"Ladies suffer like maidser- 
vants. . . . Then he who would 
have smitten the evil, stretched 
out his arm agajnst it, would 
have destroyed their seed and 
their heirs." 



Confluence of God's will 



Anthrax 



An earthquake 



Famine secondary to 

destruction of wheat and 

spett harvests 

Mycotoxm-induced death 
from moldy feeds 



Typhokt fever and 

salmonelloses 

(S. TyphV and entenditrs) 



Schistocerca gregaria eat all 

remaining vegetation, including 

sprouts and seedlings 



Sandstorms (khamsin) 
cover existing food stands 
and stored food supplies 



Mycotoxins specific to 
stored grains preferentially 
killed first to access store 



John S. Marr and Curtis D. Malloy 13 



Unlike such bloodsucking insects as lice, 
those tiny, annoying hematophagous flies 
are not species-specific; they bite both hu- 
mans and animals with a vengeance, as sug- 
gested by one species name, C. vexans. Bites 
can cause severe local reactions, intense itch- 
ing, and weal formation. Until the late 1960s, 
Culicoides were considered "nuisance" ar- 
thropods, incapable of transmitting infec- 
tious agents. They are now recognized as 
biological vectors of a number of human and 
animal viral diseases. Thus we conclude that 
Culicoides was the cause of the third plague 
as well as the biological vector for the fifth 
plague. 16 

The fourth plague, the "swarm of flies," 
has been given numerous interpretations. 
Sometimes referred to as "beasts," they 
should be distinguished from the third 
plague, although some renditions of the 
plague account combine those two insects. 
Hoy te notes that the life cycle and bionomics 
of the stable fly (Stomoxys calcitrans, L.) coin- 
cides with the ebbing of the Nile in Septem- 
ber, when abundant rotting vegetation 
fosters ideal harborage for its emerging lar- 
vae. Charles Brues listed thirty-one species 
of Stomoxydinae, including S. sexvittata 
Roubaud (now S. bilneata Grueriberg). In addi- 
tion, Stomoxys nigra Macquart occurs 
throughout Africa and attacks cattle, horses, 
and people. 17 

Alternative explanations of the "swarm" 
have been the housefly (Musca), tsetse fly 
(Glossina), horsefly (Tabanus), and blackfly 
(Simulium). The housefly does not bite. The 
other three are biters and bloodsuckers, ca- 
pable of causing severe pain, local irritation, 
inflammation, and itching. In only two of the 
fly genera, Glossina and Stomoxys species, do 
both the male and female take blood meals. 
Bites of both flies necessitate ripping of flesh, 
often leaving open puncture wounds, lead- 




Ancient Egyptian pictograph of a stable fly 

(Reproduced with permission from John Baines and 
Jaromir Malek, Atlas of Ancient Egypt [New York: 
Facts on File, 1989]) 



ing to secondary infections. Unlike the an- 
noying sand fly, the intensity and severity of 
swarms of both tsetse and stable flies have 
been reported to induce anemia in penned 
cattle and stampedes in wild animals. All of 
the aforementioned flies are capable of 
transmitting infectious agents (vide infra), 
but only Glossina and Stomoxys appear to be 
appropriate insect vectors for either one or 
both of the subsequent two plagues. We con- 
clude that the stable fly better fulfills the role 
as the cause of the fourth plague. 

The sequelae of the first and second 
plagues appear to have generated opportu- 
nity for plagues three and four. Denied po- 
table water or water in which to bathe, the 
Egyptians and their livestock would be 
more exposed to infestation, attack, and sec- 
ondary infections. Either mechanically or 



14 Ten Plagues of Egypt 



biologically, at least one kind of fly inocu- 
lated pathogenic viral, bacterial, or proto- 
zoan organisms into animals and humans, 
causing subsequent disease. Thus, the third 
and fourth plagues might be logically linked 
to the fifth and even the sixth plague. 

Fifth and Sixth Plagues— Murrain in Animals and 
Boils and Blains 

The fifth plague is probably the first writ- 
ten record of a true epizootic — a disease in- 
flicted upon animals but not humans. A 
proper proposal should account for such 
selectivity, as should the subsequent sixth 
plague, a zoonosis, which affected both ani- 
mals and humans. Specifically, the fifth 
plague struck many hoofed animals — 
horses, donkeys, camels, cattle (including 
oxen), and sheep. Hoyte notes that the omis- 
sion of goats and pigs "is of social, not 
epidemiologic significance." 

Nevertheless, that those animals, which 
were of common occurrence in Egypt at that 
time, were not mentioned is relevant, pro- 
viding negative evidence-clues as to what 
the plague may have been. The fifth plague, 
or "murrain," appears to be specific for cer- 
tain hoofed mammals, sparing domestic 
pets and wild carnivores, as well as birds, 
amphibians, and reptiles. In addition to five 
candidate diseases proposed by previous 
authors, we propose five other lesser 
known, arthropod-borne African epizootics 
infecting hoofed mammals. 18 

Anthrax is a severe bacterial infection ca- 
pable of being transmitted by various direct 
and indirect methods, including mechanical 
transmission by biting flies. Anthrax can in- 
fect a wide range of animals, especially 
goats. Wild animals, including elephants, 
hippopotami, and impala (but not frogs, as 
suggested by Hort) can also be infected with 
anthrax. Those animals, as well as goats and 



pigs, are not listed or noted in the otherwise 
complete list of animals affected. Anthrax 
can also cause human disease; its cutaneous 
form is associated with a 5-20 percent rate 
of human mortality, an observation that pre- 
sumably would have been recorded had it 
occurred. Anthrax, we believe, is not a viable 
candidate for the fifth plague. 19 

Rift Valley fever, a viral disease transmit- 
ted by various genera of mosquitoes, also 
can cause illness in humans and may be 
similarly dismissed. Rift Valley fever causes 
illness in goats and pigs but spares horses 
(prominently mentioned as being afflicted). 
Rinderpest and foot-and-mouth disease are 
airborne viral infections, but neither affects 
horses. Two hard tick-borne rickettsial dis- 
eases, East Coast fever (Theiliasis) and heart- 
water (Coivdriosis) cause illness in cattle but 
not horses; the former does not cause illness 
in sheep, and the latter causes disease in 
goats. Another hard tick-borne disease, ba- 
besiosis, is a protozoan disease mimicking 
malaria and is capable of causing disease in 
all animals listed. As noted by Hoyte, each 
equid and ruminant has a different and spe- 
cific genus of tick vector; moreover, the tick 
vectors are large, easily recognized during 
attachment, and likely to have been noted. 20 

Surra, as proposed by Hoyte, is a proto- 
zoan disease caused by a trypanosome (T. 
brucei evansi). While responsible for disease 
limited to equids and ruminants, surra is 
mechanically transmitted by both tsetse and 
stable fly bites. Tsetse fly distribution does 
not extend into northern Egypt, however, 
and while stable flies are cosmopolitan, the 
disease's present enzootic range in Africa 
suggests that it has never penetrated more 
than 15 north of the equator. 

The last two diseases, African horse sick- 
ness and bluetongue, are caused by viruses 
belonging to seventeen different serological 



John S. Marr and Curtis D. Malloy 15 



subgroups in the genus Orbivirus. Those two 
RNA viral diseases are biologically trans- 
mitted by the same genus, the Culicoides 
midge. African horse sickness is extremely 
lethal in horses, donkeys, mules and other 
equines, with a case fatality rate of 95 per- 
cent, but it spares other hoofed animals. 
Bluetongue is variably fatal for cattle, sheep, 
and goats but not for horses or pigs. Neither 
disease causes illness in humans, and they 
are therefore logical choices for the murrain 
in animals. We therefore propose that those 
two midge-borne diseases were the cause of 
the grievous fifth plague among hoofed ani- 
mals, including goats in the "flock" but not 
swine. Even though that may be an excep- 
tion to a unitary explanation, both epizootics 
best explain the selectivity of animal 
deaths. 21 

Thus, the earlier plague of lice (Culicoides 
midges) also transmitted two arboviral dis- 
eases to hoofed animals. After introduction, 
disease spread from infected animals to oth- 
ers by many other biting insects, both me- 
chanically and biologically. Over a period of 
weeks all susceptible animals would have 
become infected. Only herds and flocks of 
animals outside the distribution range of 
Culicoides (a notoriously weak flying vector) 
were spared from those epizootics — i.e., the 
land of Goshen. 

The sixth plague, consisting of boils and 
blains, struck both humans and "beasts." 
"Beasts," while not defined, is a true 
zoonosis that may or may not include some 
or all domestic and wild animals. Re- 
searchers have offered various explanations 
for that epidemic/epizootic. Blanc's and 
Hort's proposals of ulcero-glandular an- 
thrax has been alluded to previously as be- 
ing transmitted by various flies. Hoyte also 
suggested that stable flies might transmit 
combined staphylococcal-streptococcal in- 



fections — specified as "ecthyma" — to both 
animals and humans. Giovanni Ceccarelli 
proposed a variety of strains of babesia as 
the cause. The latter appears less likely for a 
number of reasons. The variety of vector- 
specific ticks that would be needed for mul- 
tiple-species transmission seems unlikely, 
and the disease presentations in man and 
animals have no dermatological symptoma- 
tology. Regina Schoental, on the other hand, 
argues that a transient immunosuppression 
due to unnamed mycotoxins caused various 
pathogenic and opportunistic bacterial skin 
infections as the putative disease and later 
sequelae. 22 

The disease must have caused severe, 
suppurative skin infection. Both anthrax 
and a combined staphylococcal-streptococ- 
cal infection fulfill that condition. Both can 
be transmitted by flies, direct contact, or 
contaminated food and milk. Spores of an- 
thrax may also be airborne, causing a sepa- 
rate, clinical presentation — mediastinitis. A 
combined staphylococcal-streptococcal in- 
fection is not considered transmitted by the 
airborne route. A more viable bacterial can- 
didate not previously considered is glanders 
(Pseudomonas mallei, farcy), a highly conta- 
gious, airborne zoonotic bacterial disease 
transmitted by direct contact or through fly 
bites. First described by Aristotle in 330 
B.C.E., glanders is presently found through- 
out the Middle East and Africa. It is primar- 
ily a respiratory infection of horses, 
donkeys, mules, and goats (cattle are resis- 
tant to infection), with lymphatic and metas- 
tatic spread to other organs, including the 
skin or hide. Cutaneous manifestations in 
equids consist of "cord-like thickening of 
subcutaneous lymphatics along which are 
distributed chains of nodules, some of 
which are ulcerated." Human disease con- 
sist of "nodular eruptions on the face, legs, 



16 Ten Plagues of Egypt 



arms, involvement of the nasal mucosa and 
later pyemia and metastatic pneumonia." 21 
Whatever the sixth plague — in our opin- 
ion, most likely glanders — or the mode by 
which it was primarily spread — most likely 
airborne — it may have been further propa- 
gated by the ingestion of tainted meat. The 
major consequence of the plague was fur- 
ther reduction of the protein supply (meat 
and milk), which had already been danger- 
ously reduced by a fish kill. Again, the He- 
brews' animals living in Goshen were 
spared both the fifth plague (African horse 
sickness and bluetongue) and sixth plague 
(glanders). 

The Seventh and Eighth Plagues— Hail and 
Locusts 

Hail occurs throughout the temperate and 
tropical worlds, usually seasonally. Caused 
by collisions of supercooled water in cumu- 
lonimbus clouds, hailstones may have a di- 
ameter of 2mm to 13cm (1/1 6th inch to five 
inches). Larger hailstones have killed unpro- 
tected humans and animals; smaller stones 
can still cause severe damage and destruc- 
tion to smaller animals and to crops. The hail 
described in the biblical account would have 
been certainly severe enough to kill or maim 
both humans and animals caught in the 
fields. More important, the hailstorms 
would have devastated the seasonal fruit, 
vegetable, and grain crops of the Egyptians 
at a time when they depended on their yield 
to last through the following year. That was 
the antepenultimate assault on the Egyp- 
tians' existing food supply, which would be 
further tested by the eighth plague, whence 
Egyptians would have to rely on their mea- 
ger reserves. 

The desert locust (Schistocerca gregaria) is 
specific to Africa, the Middle East, and India; 
it may occur in swarms and persist in a 



region for as long as several years. That 
those insects were known and revered, if not 
feared, is recorded on ancient Egyptian 
friezes predating the plagues. Transformed 
from solitary grasshoppers by as-yet-un- 
explained factors (presumably food-de- 
pendent), locusts swarm and become 
"gregarious," attacking all known standing 
crops. They consume all plant crops and 
seedlings, acting to cleanse an area of all 
living vegetation, whether food or not. The 
locust swarms, coming soon after the plague 
of hail — which would have damaged fruit- 
trees and vegetable crops — would have pre- 
cipitated great urgency on the part of the 
Egyptians to save their fallen, wilting 
stands. Partially damaged crops would have 
been hastily carried to protected sheltered 
granaries and underground storage facili- 
ties. The crops would have been broken and 
dampened by hail, damaged by immersion 
in fields, and contaminated by insect feces 
(rich in bacterial and fungal microorgan- 



isms 



24 



The Ninth and Tenth Plagues— Darkness and 
Death of the Eldest 

However darkness reigned over Egypt for 
three days and nights, it prevented Egyp- 
tians from leaving their homes or even mov- 
ing within their homes. The Hebrews in 
Goshen were not affected by the ninth 
plague. Hort acknowledges Georg Ebers's 
proposal that a volcanic eruption may have 
accounted for the phenomenon, but she noted 
no corroborative evidence. The same might 
be said for Velikovsky's theory of "gravel" 
from a passing comet. Hort's proposal that 
the darkness was due to a khamsin, a hot 
southerly wind coming from the Sahara, is 
most convincing. She suggests that the fierce, 
hot winds would have picked up ultrasmall 
particles of sand, creating a sandstorm so 



John S. Marr and Curtis D. Malloy 17 



massive that it nearly eclipsed the sun in a 
dark yellow haze. She notes that the particu- 
lar khamsin causing the sandstorm would 
have to be the first of many experienced in 
Egypt during khamsin season (March 
through May), which is in keeping with her 
timetable that the ninth plague must have 
occurred in March. The first of those sea- 
sonal windstorms would be the worst, pick- 
ing up all accumulated fine sand from the 
previous year; once deposited on land, the 
sand would cause massive drifts and dunes 
of ultrafine sand in the lees of houses, mak- 
ing entrance and egress impossible. Severe 
storms (sobaa) commonly last for two or 
three days, covering small houses and shel- 
ters. Years and decades of seasonal khamsins 
cause the disappearance of ancient monu- 
ments, tombs, and cities that archaeologists 
are continuing to discover in the upper Nile 
region of Egypt. 25 

Hort is strangely cursory in her explana- 
tion of the tenth plague, offering little in the 
form of exegesis. She considered the plague 
an extension of the previous nine plagues in 
bringing the Egyptian Empire closer to star- 
vation. A novel interpretation offered is that 
"first-born" may have been an inadvertent 
translation of the Hebraic first-born n33 for 
first-fruits D'133 . She suggested that the 
Hebrew people, who had normal stores of 
"corn," anticipated a conflict with Egyp- 
tians. The Egyptians were bereft of food (fish 
and meat), crops (wheat, barley, emmer, 
spelt, fruit), and even the ability to till soil 
(due to the death of the beast of burden). 
They could not expect new crops due to the 
destruction of crops and new seedlings by 
the preceding hailstorms and locusts. The 
ninth plague — a sandstorm — covered the 
remaining tillable land. 26 

Alternative explanations also build on the 
accumulative disruptions either exclusively 



inflicted upon only Egyptians — the fourth, 
fifth, sixth, seventh, and ninth plagues — or 
Egypt as a whole (including Goshen), the 
first, second, third, and eighth plague. Spe- 
cific diseases (e.g., anthraxm or typhoid), or 
catastrophes (e.g., an earthquake) may, in 
part, explain preferential deaths of Egyp- 
tians since Goshen was geographically sepa- 
rate and spared from those occurrences. 
Those explanations are nevertheless limited. 
First, the symptoms of anthrax — cutaneous 
or pulmonic — are fairly dramatic, as is the 
destruction brought on by an earthquake. If 
the account of the Ten Plagues included 
boils and blains and a hailstorm, one would 
argue that a description of the symptoms 
and events around the tenth plague would 
also have been offered. Neither an anthrax 
epidemic nor an earthquake are in concert 
with previous plagues, building as they did 
on a theme of an impending famine caused 
by a decreasing supply of food. 27 

Hort's suggestion that death of the first- 
fruits (i.e., sprouts) may have been, more 
than figuratively, the final insult. The cata- 
clysmic consequences of the last and most 
serious plague (the death of an estimated 10 
percent of all humans and animals) is not 
studiously considered by Hort. Hoyte, by 
contrast, in considering the sequelae of a 
compromised food supply, offers an expla- 
nation of a form of food poisoning from 
contaminated foodstuffs (consumed by hu- 
mans and animals) as a possible cause. The 
specific infections causing the epidemic and 
zoonosis proposed by Hoyte are, respectively, 
typhoid fever (Salmonella typhi) and salmonel- 
losis (Salmonella typhimurium). Those two in- 
fections are posited because the former does 
not cause illness in animals and the latter 
causes infection in both man and animals. 
They have different incubation periods 
(weeks for typhoid, days for salmonellosis). 



18 Ten Plagues of Egypt 



Both infections have different gastrointesti- 
nal and extragastrointestinal presentations. 
Both may cause death, but only after many 
days or weeks of illness — not immediately. 28 
Possible clues to the cause of the tenth 
plague include (1) its unitary nature, (2) the 
very lack of a description given to it, and (3) 
its sudden nature. Aside from an immediate, 
overnight death of large numbers of eldest- 
born humans and animals throughout 
Egypt, no symptoms are recorded. As with 
anthrax, typhoid, salmonellosis, babesiosis, 
and an earthquake, an infectious disease or 
natural calamity usually has physical mani- 
festations that might be expected to be noted 
and recorded. Only if man and beast were to 
be suddenly, and quite literally, dropped in 
their tracks, within minutes or hours after 
exposure, would one expect no description 
of prodromata, symptoms, or a prolonged 
clinical course. If such a single cause is of- 
fered and is in keeping with that premise, it 
should also take into consideration the influ- 
ence of the previous nine plagues. Finally, it 
should explain the preferential death of the 
eldest human and animal. 

Hypothesis for the Cause of the Tenth Plague 

Such an explanation for the tenth plague 
does exist, but its very existence was not 
known until a few years ago. What follows 
is a review of the preceding plagues and 
their consequences: 

• The freshwater supplies of the upper 
Nile Delta were made undrinkable and, 
months later, suspect. 

• Fish, an important supply of protein, 
were lost for a time; they, like the water, 
were considered a suspect source of 
food. 

• Frogs died, allowing insects to multiply 
unheeded. 




• Animal protein from cattle, sheep, 
goats, and swine were demonstrably 
tainted or reduced through illnesses. 

• Such draft animals as horses, donkeys, 
and oxen were afflicted, and harvests 
were thus left largely unattended. 

• Field crops were destroyed by hail and 
water, left to rot, or picked hastily. 

• Locusts consumed the remaining vege- 
tation, particularly young shoots that 
might have offered the hope of new 
crops. 

• A sandstorm covered all obvious re- 
maining sources of food supplies, and 
provided a blanket of warmth, humid- 
ity, and darkness for water-soaked 
foodstuffs buried beneath the sand to 
rot. 

• The 2.5 million people of the Egyptian 
nation were starving after ten months of 
ill fortune. 

• A mysterious affliction then killed the 
eldest Egyptian and the eldest of ani- 
mals in a sudden strike, without any 
explanation other than Yahweh's will. 

Would any known natural phenomenon 
explain the above? Noteworthy is Schoental, 
who first suggested that mycotoxins in con- 
taminating stored foodstuffs could explain 



Egyptian 
hieroglyphics 

(Reproduced with 
permission from 
William j. Darby, 
Paul Clialioun- 
giii, and Louis 
Grivetti, Food: 
The Gift of 
Osiris [New 
York: Academic 
Press, 1977]) 



John S. Marr and Curtis D. Mallov 19 



the sudden death of Egyptian males and 
animals. In a brief paragraph from a larger 
exposition, "Mycotoxins in the Bible," she 
suggested that the most dominant humans 
and animals probably had the earliest access 
to the stored, moldy food supplies, which of 
course were fatal. The nature of those food 
supplies, the specific mycotoxin(s) infecting 
them, the specific cause(s) of death, and the 
logical explanation of a lack of symptoms for 
those deaths could not be addressed, how- 
ever, as the causative agents had yet to be 
identified. 29 

Very much like species-specific arthropod 
vectors and host-specific disease agents, 
mycotoxin-producing fungi are also plant- 
specific in foodstuffs they attack. Toxins 
produced by those fungi also vary in mu- 
tagenic, carcinogenic, and toxicologic prop- 
erties. By analyzing foodstuffs available to 
Egyptians (and their animals) at the time of 
the Exodus, one may be able to identify 
likely candidate mycotoxins that may have 
caused sudden illness in both humans and 
livestock. 30 

Egyptian foods and food reserves have 
been well documented. Indeed, William J. 
Darby and his colleagues state that the sec- 
ond most important and powerful position 
in the Egyptian government was keeper of 
the granaries because periodic famine had 
instilled careful planning on the part of the 
pharaohs. Most crucial of all foodstuffs were 
the grains, specifically barley and wheat. 
The early precursors of what today is called 
"wheat" were, during the second millen- 
nium B.C.E., the precursor grains, spelt and 
emmer. Other grains in evidence at that time 
were sorghum, rye, and "corn." 31 

During the time of Thutmose III, barley 
was largely used to make a primitive beer. 
Spelt and emmer was used to make bread, 
and stored as a commodity for future need 



or trade. Sorghum was either limited in use 
or used for trade. Rye was not yet intro- 
duced. "Corn," as translated by the Scrip- 
tures, must have been any early form of 
wheat since true "corn" (maize), as we know 
it, is a New World vegetable. The talmudic 
and biblical terms "corn" must, by force, 
signify a wheatlike product, perhaps emmer 
or spelt. A distinction among those grains is 
important, since it allows a differential 
analysis to be made regarding mycotoxins. 

More than one hundred toxigenic fungi 
have been identified since the first myco- 
toxin, aflatoxin, was discovered in 1961. 
Dozens have been identified as causing 
natural outbreaks in human and animal 
populations; only a few, however, have been 
traced to standing or stored grains of eco- 
nomic importance used for food and fodder. 
The specific genera of those fungi are 
Claviceps, Aspergillus, Penicillium, Fusarium, 
and a variety of lesser organisms. The most 
potent mycotoxins within those four genera 
that are specific for wheat are the stachybotryo- 
toxicoses produced by Fusarium graminearutn 
and Stachybotrys atra. The mycotoxins pro- 
duced (macrocyclic trichothecenes) have 
been linked to the deaths of thousands of 
people and animals in the former USSR dur- 
ing World War II, as well as a variety of 
livestock (poultry, cattle, horses, sheep, and 
swine) in many countries. Humans ingest 
products from grain, such as bread; poultry 
eat grain, equids consume fodder, and rumi- 
nants (cows, oxen, and camels) eat straw. (Of 
interest, ruminant animals are preferentially 
attracted to damp straw on which S. atra 
grows.) 32 

More recently, S. atra mycotoxins caused 
illness and deaths in humans who have had 
no direct contact with mycotoxins other than 
inhaling them. Trichothecene mycotoxins 
produced on walls and basement floors in 



20 Ten Plagues of Egypt 



j rr ir rrg 



= 



He gave them 




hail 


- stones fc 


r 


rain ; 






o 




tire 








» * 










^ m 






r 




r 








w 


^ 






























i 













He gave them hail - stones tor tain 



r r r i mUiLj i r££frj g i P fLgj 



s 






mrrogflg^ 



i 



r r > ' '' rg 



s 



^-J3Q 



Handel's interpretation of the plague of hail, in Israel in Egypt 



water-damaged buildings were carried to 
their victims through ventilation systems. A 
similar exposure in a farming couple caused 
bronchiolitis in the man and acute renal fail- 
ure in the woman, both of whom had been 
working in a silo and were exposed to Asper- 
gillus ochraceus. Mycotoxins have also been 
hypothesized as an explanation for illness 
and death among archaeologists, made fa- 
mous in the so-called "King Tut's curse." 33 
(The Earl of Carnarvon, discoverer of King 
Tut'ankhamun's tomb, died of unexplained 
pneumonia in 1922.) 

Although macrocyclic trichothecenes 
vary in toxicity and cytotoxicity in labora- 
tory animals, it is apparent that very small 
amounts cause illness and death. Fusty, di 
minimis amounts of S. <?fra-induced myco- 
toxicosis are now being recognized as a pos- 
sible cause of "sick-building syndrome." 
Chronic low exposures can cause (as origi- 
nally suggested by Schoental) granulocy- 
topenia and increased susceptibility to 



bacterial infection. Acute, large exposures 
cause immediate symptoms of gastrointesti- 
nal irritation, petechial hemorrhage, and 
massive internal bleeding, resulting in sud- 
den death. 34 

Conclusion 

The sudden death of Egyptian people and 
their animals may be due to the precipitous 
raid of improperly stored grains, fodder, 
and foodstuffs. Elder, more responsible, or 
more powerful individuals would have had 
first access to granaries and may have in- 
haled aerosolized S. atra mycotoxins. Those 
people would also be first to eat the breads 
or drink the beer produced from the moldy 
wheat and barley, respectively. Similarly, 
the more dominant animals would eat grain 
and straw on which a patina of mycotoxin- 
producing fungi grew. Soon thereafter, 
acute symptoms and sudden deaths ma)' 
have alerted both man and animal of the 
danger in ingesting the grains and grain 



John S. Marr and Curtis D. Malloy 21 



products. Subsequently, once granaries had 
been aired, the inhalational route was no 
longer a factor. In addition, deeper stores of 
wheat and barley may have not been as 
heavily contaminated by the surface-grow- 
ing fungi, and therefore, relatively safer to 
eat — sparing less powerful man and beast. 
The Hebrews in Goshen, who had experi- 
enced neither the calumny of tainted fish 
and meat nor the destruction of crops, nor 
famine, would also have avoided the mass- 
poisoning due to those mycotoxins. 

That, then, is our explanation for the most 
devastating, tenth and last plague of Egypt, 
and the proceeding plagues that may have 
contributed to it. Numerous theologians 
and biblical scholars have authored pre- 
vious, significant, original, and unique con- 
tributions to the eclectic interpretation of 
causes of the Ten Plagues (most notably 
Hort, Hoyte, and Schoental). We greatly ac- 
knowledge their hypotheses and add our 
interpretation and a final synthesis to that 
impressive collection of literature. It is a 
tragic and powerful story of two proud peo- 
ples — the Egyptians, under Thutmose III at 
the height of their empire, and the people of 
Israel about to become a nation. We hope 
that others might wish to begin where we 
concluded, and to follow with their own 
interpretations. 

We end with this note: The long Jewish 
tradition about the first Passover began at 
the end of the ninth plague. It is a celebration 
of the first meal to mark the Hebrews' escape 
from the many plagues, and from the tenth 
plague. The Passover celebration consists of 
eating symbolic newborn, healthy lamb 
shank, fresh herbs, and horseradish — all 
safe from mycotoxin exposure. It also re- 
quires eating unleavened bread made from 



fresh flour, which is, by definition, free of 
any yeasty or other mycotoxin contamina- 
tion. 



Notes 



1 . Curtis. D. Malloy et al., "Emerging Pathogens: 
The White Horse of the Apocalypse?" Journal of Pub- 
lic Health Management and Practice 1 (1995): 48-61; 
Mary E. Wilson, Richard Levins, and Andrew Spiel- 
man, eds., Disease in Evolution: Global Changes and 
Emergence of Infectious Diseases, vol. 740, Annals of the 
New York Academy of Sciences (New York: Acad- 
emy of Sciences, 1994), 1-503. 

2. All references are to the Authorized (King 
James) Version. 

3. Immanuel Velikovsky, Worlds in Collision 
(Garden City, N.Y.: Doubleday, 1950), 49; Velik- 
ovsky, Ages in Chaos (London: Sphere Books, 1973), 
41-44; "The Admonitions of Ipuwer, Papyrus 
Leiden 344, Recto," in Ancient Egyptian Literature: A 
Book of Readings, ed. Miriam Lichtheim, 3 vols. 
(Berkeley: University of California Press, 1973), 
1:149-63. 

4. Greta Hort, "The Plagues of Egypt," Zeitschrift 
fur die Altesttamentliche Wissenschaft 69 (1957): 84-103; 
Hort, "The Plagues of Egypt," Zeitschrift fur die Al- 
testtamentliche Wissenschaft 70 (1958): 48-59. 

5. Donovan A. Courville, Tlie Exodus Problem and 
Its Ramifications (Loma Linda, Calif.: Challenge 
Books, 1978), 116-32; Tlie Ten Commandments, Para- 
mount Pictures, Hollywood, Calif., 1956; Werner 
Keller, The Bible as History (New York: William Mor- 
row and Co., 1981), 122; H. M. D. Hoyte, "The 
Plagues of Egypt: What Killed the Animals and First- 
born?" Medical Journal of Australia 158 (1993): 706-8; 
John J. Bimson, Redating the Exodus and tlw Conquest 
(Sheffield, Eng.: Almond Press, 1981); John Baines 
and Jaromir Malek, Atlas of Ancient Egypt (New York: 
Facts on File, 1989), 36. 

6. Baines and Malek, Atlas, 36. 

7. Martin Gilbert, Jewish History Atlas (London: 
Weidenfeld and Nicolson, 1976), 312; Courville, Exo- 
dus Problem, 116-32. 

8. It is interesting that Isaac Asimov, in his com- 
prehensive Asimov's History of tlie Bible: The Old Tes- 
tament, provided no interpretation regarding the Ten 
Plagues. See Asimov's History of the Bible: The Old 
Testament (New York: Doubleday, 1968), 1-1295. 



22 Ten Plagues of Egypt 



9. Jacob Bryant, Observations upon tlie Plagues In- 
flicted upon the Egyptians (London: Hamilton and H. 
Ogle, 1810), 1-392. Velikovsky's book and his theo- 
ries cannot be expanded upon here. However, it 
must be noted that his hypothesis about a comet and 
its subsequent damage, ostensibly incredulous when 
he wrote his book in 1950, may be partially substan- 
tiated by "Bits of Mars Hit Africa in '62, Researchers 
Say," New York Times, March 31, 1995, A16, which 
suggests that an explosion on Mars millions of years 
ago produced material that landed on Earth at least 
three times, the most recent of which was in Nigeria. 
Furthermore, Velikovsky's belief that a volcanic 
eruption might have served as one of many cataclys- 
mic catastrophes causing the plagues of Egypt is 
supported by a 1783 volcanic eruption described in 
Stuart Flexner with Doris Flexner, Tlie Pessimist's 
Guide to History (New York: Avon Books, 1992), 95. 

10. P. A. Tester, "Harmful Marine Phytoplankton 
and Shellfish Toxicity: Potential Consequences of 
Climate Change," in Disease in Evolution, 69-76; E. C. 
D. Todd, "Emerging Diseases Associated with Sea- 
food Toxins and Other Water-Borne Agents," in Dis- 
ease in Evolution, 77-94; Wayne W. Carmichael and 
Ian R. Falconer, "Diseases Related to Freshwater 
Blue-Green Algal Toxins and Control Measures," 
Algal Toxins in Seafood and Drinking Water, ed. Fal- 
coner (London: Academic Press, Ltd., 1993), 188-209; 
JoAnn M. Burkholder, H. B. Glasgow, and Karen A. 
Steidinger, "Unravelling Environmental and Tro- 
phic Controls on Stage Transformations in the Com- 
plex Life Cycle of an Ichthyotoxic 'Ambush Predator' 
Dinoflagellate," abstract from the Sixth International 
Conference on Toxic Marine Phvtoplankton, Nantes, 
France, Oct. 18-22, 1993. 

11. William J. Darby, Paul Ghalioungui, and 
Louis Grivetti, Food: The Gift of Osiris, 2 vols. (New 
York: Academic Press, 1977), 1:337. 

12. Personal communication from Richard L. 
Brown, Ph.D., Curator, Mississippi Entomological 
Museum, Mississippi State Universitv, July 24, 1995; 
Defense Pest Management Information Center, Dis- 
ease Vector Ecology Profile: Egypt, Technical Informa- 
tion Bulletin (Washington, D.C.: Forest Glen Section, 
Walter Reed Army Medical Center, 1988), 1-48. 

13. Personal communication from David J. 
Sencer, M.D., M.P.H., Centers for Disease Control 
(retired), July 27, 1995. 

14. Hoyte, "Plagues of Egypt," 706-8. 

15. Disease Vector Ecology Profile. 

16. Maurice T. James and Robert F. Hanvood, 
Herms's Medical Entomology, 6th ed. (New York: 
Macmillan and Company, 1969), 161-64. 

17. Hoyte, "Plagues of Egypt"; Charles T. Brues, 
"Geographic Distribution of tlie Stable Fly, Stomoxys 
calcitrans," journal of Economic Entomology 6 (1913): 
459-77; Brown communication. 

18. Hoyte, "Plagues of Egypt," 706-8. 

19. Abram S. Benenson, ed., Control of Communi- 
cable Disease in Man (Washington, D.C.: American 
Public Health Association, 1990), 17. 

20. Committee on Foreign Animal Diseases, For- 
eign Animal Diseases (Richmond, Va.: United States 



Animal Health Association, 1992), 1—424; Benenson, 
Control of Communicable Disease, 54; Paul F. Crane- 
field, Science and Empire: East Coast Fever in Rhodesia 
and the Transvaal (Cambridge, Eng.: Cambridge Uni- 
versity Press, 1991), 1-385. 

21. Committee on Foreign Animal Diseases, For- 
eign Animal Diseases. According to Rabbi Nosson 
Scherman, the fifth plague could not have killed all 
the animals of Egypt (as verse 6 states) but only the 
animals in the field. Spared were all animals in 
Goshen, sheltered Egyptian ruminants and equids, 
and domestic household pets. That interpretation 
facilitates the explanation of the next epidemic, 
when both humans and surviving "beasts" were 
afflicted. It also allows for a solution to the question 
of where the pharaoh obtained the horses necessary 
to pursue the Hebrews during the subsequent Exo- 
dus. Scherman, Tlie Chumash: The Torah: Haftaros and 
Five Megillos with a Commentary Anthologized from the 
Rabbinic Writings, ArtScroll series (Brooklyn: 
Mesorah Publications, Ltd., 1993), 1-313. 

22. Hort, "Plagues of Egypt," 69: 84-103, and 70: 
48-59; Henry W. Blanc, Anthrax: The Disease of the 
Egyptian Plagues, rpt. from Neiv Orleans Medical and 
Surgical journal, July 1890; G. Ceccarelli, "Le dieci 
piaghe d'Egitto e la loro interpretazione medica," 
Minerva Medica 85, no. 5 (1994): 271-77; Regina 
Schoental, "A Corner of History: Moses and Myco- 
tox&&" Preventive Medicine 9 (1980): 159-61; Schoen- 
tal, "Mycotoxins and the Bible," Perspectives in 
Biology and Medicine 28 (Autumn 1984): 117-20. 

23. Committee on Foreign Animal Diseases, For- 
eign Animal Diseases. 

24. Robert A. Cheke and Johnson Holt, "Complex 
Dynamics of Desert Locust Plagues," Ecological En- 
tomology 18 (1993): 109-15; Darbv et al„ Food, 1:337. 

25. Hort, "Plagues of Egypt,'" 70: 48-59; Velik- 
ovsky, Worlds in Collision; personal communication 
from W. Benson Harer, Jr., physician and Egyptolo- 
gist, July 20, 1995. 

26. Hort, "Plagues of Egypt," 70: 48-59. 

27. Velikovskv, Worlds in Collision; Vehkovsky, 
Ages in Clmos; Hort, "Plagues of Egypt," 69: 84-103 
and 70: 48-59; Benenson, Control of Communicable 
Disease, 17; Schoental, "Corner of History," 159-61; 
Ludwig Schmidt, Beobachtungen :u der vlagenerza- 
hlung in Exodus V1I14-XI W (Leiden: E. J. Brill, 1990), 
1-23; M. G. Jacoby, "The Fifth Plague of Egypt," 
journal of the American Medical Association 249 ( 1983): 
2779-80'. 

28. Hoyte, "Plagues of Egypt," 706-8; Benenson, 
Control of Communicable Disease, 469, 381. 

29. Schoental, "Corner of History," 159-61; 
Schoental, "Mycotoxins," 117-20. 

30. Raghubir P. Sharma and Dattajirao K. Sa- 
Lunkhe, Mycotoxins and Phytoalexins (Boca Raton, Ha.: 
CRC Press, 1991), 68-73. " 

31. Darby et al., Food, 457-99. 

32. Sharma and Salunkhe, Mycotoxins, 68-73; D. 
Carleton Gajdusek, Alimentary Toxic Aleukia in Acute 
Infectious Hemorrhagic Fevers and Mycotoxins in the 
Union of Soviet Socialist Republics, Medical Science 
Publication, no. 2 (Washington, D.C.: Army Medical 



John S. Marr and Curtis D. Malloy 23 



Service Graduate School, Walter Reed Army Medi- 
cal Center, 1953), 34. 

33. W. A. Croft, "Airborne Outbreak of Tricothe- 
cene Toxicosis," Atmospheric Environment 20 (1986): 
542-52; personal communication from Eduardo 
Montana, M.D., Centers for Disease Control and 
Prevention, Atlanta, June 25, 1995; N. DiPaulo et al, 
"Inhaled Mycotoxins Lead to Acute Renal Failure," 
Nephrology Dialysis Transplantation 9, suppl. 4 (1994): 
116-20. 

34. Sharma and Salunkhe, Mycotoxins, 1-775; 
Eckardt Johanning, "Health Problems Related to 
Fungal Exposure: The Example of Toxigenic Stachy- 
botrys Chartrum Atra," Fungi and Bacteria in Indoor 
Air Environments, ed. Johanning and C. S. Yang (New 
York: Eastern New York Occupational Health Pro- 
gram, 1995), 169-82. 



JOHN S. MARR is Medical Director of M.D. Health 
Plan, a health maintenance organization based in 
North Haven, Connecticut. A graduate of Yale 
University, he earned an M.D. from New York Medical 
College and a master's degree in public health from 
the Harvard School of Public Health. He is board 
certified in internal medicine, preventive medicine, 
and occupational medicine. Previously he served as 
Director of the Bureau of Preventable Diseases and 
Principal Epidemiologist in the New York City 
Department of Public Health. The author of three 
books on children's health, he is coauthor of Black 
Death (Dutton and Ballantine), a novel about bubonic 
plague, and has completed a second novel on the 
contemporary equivalents of the Egyptian plagues. 



ACKNOWLEDGMENTS 

The authors would like to acknowledge Richard L. 
Brown, W. Benson Harer, Jr., Eduardo Montana, and 
David J. Sencer, whose communications enriched this 
paper. They also acknowledge the following 
individuals, who greatly assisted their efforts in 
locating citations, reviewing the manuscript, and 
providing additional information and assistance: Louis 
N. Sorkin, R.P.E., Department of Entomology, 
American Museum of Natural History; Roger Breeze, 
D.V.M., Acting Area Director, U.S.D.A. Agricultural 
Research Service, Region II, Athens, Ga.; Kathleen A. 
Hanlon, D.V.M., Ph.D., Deputy State Public Health 
Veterinarian, Zoonoses Program, New York State 
Department of Health, Albany; John P. Woodall, Ph.D., 
Director of Arbovirology Laboratory, Wadsworth 
Laboratories, New York State Department of Health; 
Rabbi Harvey Goldscheider, Temple Beth El, North 
Bellmore, N.Y.; Stephen Berger, M.D., Chief, Infectious 
Diseases, Medical Center Tel-Aviv Ichilov Hospital, 
Tel-Aviv, Israel; Helen Hubbard Marr, New York State 
Council of the Arts; John D. Debbie, D.V.M., Chief 
Veterinarian, New York State Department of Health; 
Roberta L. Jainchill, New York State Department of 
Health, Bureau of Tuberculosis Control, Metropolitan 
New York Regional Office; John Klein, Ph.D., 
University of Missouri at Columbia; Diane E. Monroe; 
Sandra M. Gould, M.I.A.; and Leo Cuccia and Anne von 
Stulpenagel for their translations of Italian and German 
medical journal articles. 



CURTIS D. MALLOY received the baccalaureate from 
Pacific Lutheran University and the Master of Public 
Health degree from Columbia University. He is a 
Research Associate with Medical and Health Research 
Association of New York City, Inc. His research 
interests include epidemiology, infectious disease, 
and international health. 



24 Ten Plagues of Egypt 



Cholera: Outlook for the Twenty-First 
Century 



John P. Craig 



Cholera is at once the best understood of 
infectious diseases and also the most 
unpredictable in its appearance in time and 
place. Treatment is among the most success- 
ful in all of medicine, yet prevention is diffi- 
cult to achieve. An approximation of the 
sketchy history of cholera epidemics and 
pandemics of the nineteenth and twentieth 
centuries as recorded by Western observers 
is shown in Figure 1. 

Asiatic cholera was first recognized by 
Western medicine in the second decade of 
the nineteenth century, and medical histori- 
ans have recorded seven pandemics since 
then. A quick scan of Figure 1 might suggest 
to the skeptical observer that the division of 
the human cholera experience into seven 
pandemics has been quite arbitrary because 
it shows pretty clearly that since 1817 we 
have been in the throes of cholera epidemics 
more often than not. What is most fascinat- 
ing and still unexplained is that there have 
been occasional periods during which chol- 
era seemed to vanish from all parts of the 
Western world — at least to undetectable lev- 
els — and then resurfaced in unanticipated 
regions. No other infectious disease capable 
of causing such high rates of morbidity and 
mortality has exhibited that manner of re- 
current epidemic explosiveness following 
near-total disappearance from all parts of 
the world except for its permanent annual 



Pandemic and Epidemic Cholera: 1817-1995 



VI 



| Europe 

erica ( via 
v Orleans 



Africa 
Eu'ope 

America 



Egypl 

Russia 

Wesiern Europe 
England 



1937 
1940 



1945 
1947 



VII 



I "" :;l 



I Central 

i 

H — 



El Tor 
Biotype 
01 Serotype 



0139 
Serotype 



Fig. 1. Years and regions 
of the Seven Cholera 
Pandemics. 



presence in the Gangetic delta of the Indian 
subcontinent. 

Three Steps Forward 

During the era shown in Figure 1, lasting 
more than a century and a half, there have 
been three major bursts of enlightenment 
concerning the disease. The first recognized 
its contagious nature; the second revealed 



CADUEUS ♦ Spring 1996 ♦ Vol. 12. No. 1 



the microbial agent responsible; and the 
third, coincident with the current Seventh 
Pandemic, has disclosed the essential 
mechanisms of pathogenesis and has pre- 
scribed an astonishingly effective therapy. 
Unlike several other human scourges in 
which pathogenesis and treatment have 
been elucidated much less successfully, 
however, cholera has defied our attempts to 
develop a truly effective and applicable im- 
munizing agent. It still eludes our efforts to 
understand the factors that determine its 
periodic emergence in epidemic form. Chol- 
era stands in striking contrast to smallpox, 
in which the most eminently successful of all 
vaccines was perfected, applied, and led to 
the eradication of the disease before the 
mechanisms of pathogenesis were fully un- 
derstood (and before any treatment of sig- 
nificance had been devised). 

All three bursts of enlightenment in chol- 
era followed on the heels of a new pandemic 
that provided investigators with an abun- 
dance of patients and the opportunity to 
study them. 

The first was John Snow's recognition of 
the contagious nature of the disease and its 
dependence on drinking water for entry into 
the human host. 1 Snow postulated during 
the 1854 cholera epidemic in London that a 
materia morbis capable of replicating in the 
human host was transferred from one pa- 
tient to the next in the diluted liquid dis- 
charges that found their way into the water 
distribution system. Snow also proposed 
that once the entity had reached the bowel 
of the next victim it multiplied and pro- 
duced a poison that caused the bowel to 
secrete its normal intestinal juice in prodi- 
gious quantities, thus leading to the well- 
known voluminous secretory diarrhea and 
hypovolemic shock that characterizes the se- 
vere form of the disease. Snow's series of 



observations and his brilliant and simple 
exposition of his findings represented a fun- 
damental leap into a new dimension of un- 
derstanding of infectious disease, decades 
before the microbial era. A careful reading 
of his scholarly treatise will disclose an 
astonishing prescience in his descriptions 
and in his interpretations of his findings. 

The second burst of understanding came 
with Robert Koch's discovery in Egypt dur- 
ing the Fifth Pandemic that a bacillus, which 
he dubbed Vibrio comma, is the probable mi- 
crobial agent of the disease. 2 Koch was un- 
able to fulfill the third of his own 
postulates — which he proposed as the pre- 
requisites for proof of causality of any dis- 
ease. 3 Nevertheless, he laid the foundation 
for the spate of research that followed eighty 
years later when the Seventh Pandemic re- 
kindled the curiosity of the medical world 
and led to a clearer understanding of the 
manner by which Snow's materia morbis 
could wreak such sudden havoc on its vic- 
tims. It was left to Richard B. Hornick and 
his associates at the University of Maryland 
to fulfill the third of Koch's postulates with 
landmark studies that reproduced typical 
clinical cholera in volunteers in 1971. 4 

The third burst of understanding about 
the nature of cholera was stimulated by the 
current Seventh Pandemic, which began in 
1961. Thus, since the 1960s — and continuing 
today — there has been a steady outpouring 
of research that has led to a detailed under- 
standing of the structure of Koch's kom- 
mabacillus (now renamed Vibrio cholerae) 
and of its many products — most notably the 
cholera enterotoxin, an excreted protein that 
appears to be the chief but probably not the 
sole entity responsible for the hypersecre- 
tion of succus entericus that Snow so elo- 
quently described more than a century 
earlier. 5 



26 Cholera 



Although scientific literature now 
abounds with studies dealing with the 
mechanisms of pathogenesis of cholera, it is 
my opinion that the seminal work that fired 
the imaginations of all who followed was 
that of Sambhu Nath De of Calcutta. 6 De 
showed in 1958, just before the beginning of 
the current pandemic, that the cholera vibrio 
produces an enterotoxin that is responsible 
for the dramatic fluid and electrolyte losses 
that make the disease so feared and re- 
spected. It is also abundantly clear that the 
major biomedical triumph emerging from 
the laboratory and clinical research stimu- 
lated by the massive morbidity of the Sev- 
enth Pandemic has been the near-perfection 
of the treatment of patients with cholera. It 
is an unparalleled victory in the annals of 
medicine and is the result of years of pains- 
taking clinical investigation by scores of 
physicians from many countries. Today, in 
the hands of well-trained physicians (and, 
even more notably, paramedical personnel), 
there can be a 99 percent survival of patients 
with even the most severe form of the dis- 
ease with the proper use of intravenous and 
oral fluid and electrolyte replacement ther- 
apy. In no other disease in which untreated 
patients suffer such high fatality rates can 
such dramatically successful results be even 
hoped for. That fact was triumphantly dem- 
onstrated in the present ongoing epidemic 
in South and Central America (vida infra), in 
which local physicians and other health care 
deliverers achieved just such near-miracu- 
lous salvation of life with less than one per- 
cent case-fatality rates. 

Cholera is thus unique in that at present 
the protection of human life depends upon 
treatment of the disease after onset rather 
than prevention by vaccination or interrup- 
tion of transmission. The latter may appear 
ironic upon first thought; unlike an airborne 



infection we clearly know how to disinfect 
an individual's intake of food or drink, but 
because of our ignorance of the ecology of 
vibrios in the environment, that theoretical 
knowledge cannot yet be translated into re- 
alistic protection of most of the communities 
or societies of our world. An approach that 
differs fundamentally from the control of 
smallpox or tuberculosis will be required to 
prevent cholera from recurring indefinitely 
into the future, often in epidemic propor- 
tions, in all but the minority of well-sani- 
tated societies of the world. 

By 1991, the Seventh Pandemic had per- 
sisted longer by many years than any of the 
earlier six. Having begun in 1961, it was well 
into its thirtieth year. It had spread along 
most of the major trade and travel routes in 
the footsteps of the previous epidemics 
across Asia, the Middle East, and into south- 
ern Europe. In 1970 it re-seeded sub-Saharan 
Africa for the first time in this century; 
within two years, more than thirty central 
African countries had suffered significant — 
and, in many cases, major— epidemics with 
case-fatality rates of 6 percent to 30 percent. 7 
It now appears that cholera has become en- 
demic for the foreseeable future in central 
Africa. Increased urbanization and an in- 
ability to provide enough clean water for the 
burgeoning populations have prevented 
health officials from breaking the chain of 
human-to-human spread. 

In 1973 cholera appeared along the United 
States Gulf Coast, but only as widely scat- 
tered isolated cases and clusters that did not 
lead to human-to-human spread. That strain 
of the cholera vibrio was later demonstrated 
to be quite distinct from the Eurasian and 
African strain, suggesting that, although 
temporally associated with the Seventh Pan- 
demic, it arose independently from a nonhu- 
man environmental source. * It failed to 



John P. Craig 27 



spread because the rural communities in 
which it occurred (Texas, Louisiana, and 
Florida) enjoyed better arrangements for the 
disposal of human feces than did most of the 
earlier diseased areas of Asia and Africa. 

The late 1970s and the 1980s did not wit- 
ness a significant spread of cholera to new 
areas of the globe. Medical and public health 
communities had become rather accus- 
tomed to the notion that cholera would re- 
main endemic in those communities in the 
Old World where the chain of contagion 
could not be fully broken as long as public 
sanitation suffered from an unsurmount- 
able level of stagnation. Everyone knew how 
cholera spread, and everyone knew what 
needed to be done to eradicate epidemic 
disease (if not sporadic self-limited out- 
breaks). Nevertheless, the ability to translate 
that know-how into a universal clean water 
and clean food distribution system was be- 
yond the reach of the majority of communi- 
ties in the developing nations. 

During the same period, many observers 
noted that much of Central America and 
South America suffered from a lack of public 
and private sanitation that seemed to invite 
the invasion of cholera into both rural and 
urban areas. Although most large cities had 
long ago installed water distribution, filtra- 
tion, and chlorination systems that should 
have provided an effective barrier to the 
wholesale spread of cholera, many seg- 
ments of the rapidly growing urban areas 
did not enjoy the benefits of individual 
household water and sanitation facilities. 
Some systems failed to provide adequate 
chlorination to prevent the distribution of 
pathogens to individual households. Protec- 
tion of food preparation from contamination 
by infected food handlers was often inade- 
quate. Yet, for thirty years since the begin- 
ning of the Seventh Pandemic, no confirmed 



cases of cholera were reported from any of 
the countries of Central America or South 
America. 

It was clear that that region of the world 
did not enjoy a natural barrier to the survival 
and spread of cholera, since there had been 
well-documented epidemics in the nine- 
teenth century when the earlier pandemics 
spread throughout the world. 9 Transporta- 
tion by both sea and air had expanded tre- 
mendously during the twentieth century, 
affording numerous opportunities for the 
introduction of cholera from Asia, Europe, 
or Africa during the decades in which those 
continents were being thoroughly seeded 
with the El Tor strain of Vibrio cholerae. Non- 
toxinogenic and hence nonpathogenic 
strains of the organism were repeatedly iso- 
lated from surface waters and sewers in Bra- 
zil and, if they had been looked for, could 
probably have been found in many other 
countries of the continent. No substantiated 
reason exists for supposing that ecological 
requirements for the survival and propaga- 
tion of fully pathogenic strains of the organ- 
ism differ significantly from those of 
nonpathogenic strains. The endemic patho- 
genic North American strain was no doubt 
continually present in northern coastal wa- 
ters of the Gulf of Mexico. Yet, as measured 
by historic fact, no effective introduction of 
pathogenic cholera vibrios into South Amer- 
ica or Central America took place until 1991 . 

The Latin Invasion 

In the last week of January 1991, doctors 
and public health officials of Peru were 
jolted by the sudden appearance of explo- 
sive outbreaks of cholera in three coastal 
cities. 10 The first outbreak was in the city of 
Chancay, sixty kilometers north of Lima. On 
the very next day an outbreak was reported 
from Chimbote, a seaport four hundred kilo- 



28 Cholera 



meters north of Chancay . Cases in both cities 
were bacteriologically confirmed on Janu- 
ary 31. The outbreak spread rapidly, and by 
the seventh of February there were con- 
firmed cases in at least four areas along the 
Peruvian coast from the Chilean to the Ecua- 
dorian border — a distance of more than two 
thousand kilometers. It seemed then, and 
still seems, unlikely that contiguous spread 
along land routes, even by travellers, could 
have explained the virtually simultaneous 
appearance of cholera over such a wide ex- 
panse of shoreline. By February 12, epidem- 
ics were reported from communities fifty to 
150 kilometers inland, and by February 20 
there were reported cases from the Andean 
highlands. In attempting to explain the ex- 
plosive dispersal of the infecting organisms 
that necessarily preceded the onset of dis- 
ease, at least two mechanisms can, in theory, 
be considered. 

The only mechanism that was publicly 
considered to have been operative was the 
postulated new introduction of very large 
numbers of pathogenic vibrios into Peru- 
vian coastal waters by the only source 
known capable of such delivery — namely, 
ships carrying contaminated bilge. Pan 
American Health Organization officials 
have postulated that the bacteria first ar- 
rived with a Chinese freighter, which is pre- 
sumed to have released its bilge water into 
the harbor at Lima. If that was a one-time 
introduction, how does one account for the 
fact that the first recognized cases were in 
Chancay, sixty kilometers north of Lima, 
and one day later in Chimbote, a seaport 
four hundred kilometers north of Chancay? 
Favorable climatological conditions could 
theoretically have allowed amplification at 
sea — either in open water, or following colo- 
nization of phyto- or zooplankton — leading 
to massive contamination of seafood that 



was eaten by residents of the coastal cities. 
Those patients could have subsequently 
contaminated the inadequately chlorinated 
water supply of each city, leading to a fur- 
ther amplification of transmission by the 
second route. Inland spread would have to 
be explained by the consumption of con- 
taminated seafood brought to the interior by 
surface vehicles. Feces from the first genera- 
tion of patients would then have had to con- 
taminate the local water supplies. In any 
scenario, heavy contamination of many 
separate water supply systems accompa- 
nied by totally inadequate decontamination 
before distribution would be required to ac- 
count for the high morbidity that took place 
in Peru and surrounding countries. 

Indeed, it has now been reported that dur- 
ing the 1980s many local Peruvian water 
officials decided to discontinue the chlorina- 
tion of urban wells that served as sources for 
municipal water distribution systems. 11 Af- 
ter the epidemic began, some local water 
officials cited United States Environmental 
Protection Agency studies showing that 
chlorine may create a slight cancer risk as 
justification for discontinuation of routine 
chlorination of their water supplies. It seems 
to have been a case of risk assessment gone 
wrong! 

A second possible immediate source of 
the pathogenic vibrios is one that does not 
seem to have been given serious public con- 
sideration — a sudden and massive expan- 
sion of a preexisting small population of 
pathogenic cholera vibrios on zoo- or phy to- 
plankton in Peruvian coastal waters. No 
matter how remote the possibility seems on 
first consideration, it must at least be given 
some thought. That could have occurred if a 
significant increase in the population of a 
host organism, such as occurs with certain 
algal blooms, had taken place as a result of 



John P. Craig 29 



Fig. 2. Map of 
Central and South 
America showing 
the month of onset 
of the first reported 
case of cholera in 
each country. 
Countries are 
grouped according 
to month of first 
case. 



15'- 



15- 



The Progression of Cholera through South 
and Central America 1991-1994 




Month of First Case 

Hi 1/91-3/91 

4/91 

6/91 - 11/91 

12/91 -3/92 

11/92-3/93 
I | None by 1994 



especially favorable weather and nutritional 
conditions in the far-eastern south Pacific 
Ocean. That would be consistent with simul- 
taneous appearance of the disease in a num- 
ber of coastal Peruvian cities within a very 
few days (as well as the surprisingly high 
incidence in the initial outbreaks), since 
rapid amplification of the vibrio population 
in human hosts would not be required to 



explain the first generation of victims. The 
obvious argument against such a possibility 
is the absence of recognized cholera in Cen- 
tral America and South America for over a 
century. Let us return to that hypothesis 
after further examining the course of the 
Latin American dissemination from 1991 to 
1994. 



30 Cholera 



Regardless of the nature of the initial 
source of cholera vibrios, it is clear that suit- 
able conditions for the successful introduc- 
tion and subsequent spread of cholera were 
not confined to Peru, and it is doubtful that 
all of the same human interventions (or lack 
thereof) existed in all of the countries that 
were eventually visited by the disease. 
Within three months Ecuador, Colombia, 
Brazil, and Chile had reported outbreaks of 
cholera. By August 1991, Bolivia — the last of 
the countries that share a border with 
Peru — began to experience cholera in epi- 
demic proportions. The spread of the dis- 
ease throughout Latin America is shown in 
Figure 2. A curious happening not fre- 
quently noted was the appearance of cholera 
in southern Mexico in June of the same year, 
followed by a reasonably contiguous spread 
of the disease south through Central Amer- 
ica during the latter half of 1991 . Was that an 
independent introduction, again from an 
east-Asian freighter, or was it a second 
manifestation of an amplification of vibrios 
associated with an eastern Pacific planktonic 
bloom? Does it not seem curious that within 
six months, two successful introductions of 
pathogenic Vibrio cholerac would have oc- 
curred in only one region of the globe, when 
no such phenomenon had been observed 
during more than thirty years in which the 
Seventh Pandemic of cholera had been en- 
demic in virtually all countries of east Asia 
except japan? Perhaps a careful historical 
study of the numbers of east-Asian ships 
plying eastern Pacific waters and their prac- 
tices of bilge handling would help establish 
the relative risk of such accidents having 
occurred during the preceding thirty years. 

After making its Central American debut 
in the southeastern states of Mexico in June 
1991, cholera subsequently spread to Guate- 
mala, El Salvador, Panama, Honduras, and 



Nicaragua (in that order) from July to No- 
vember of 1991. Whether that represented 
contiguous overland spread bv infected per- 
sons discharging fecal vibrios into water 
supplies, or whether seaborne introductions 
took place in each country cannot be ascer- 
tained because all except Honduras have 
Pacific coastlines. The later introduction of 
cholera into Costa Rica and Belize in January 
1992, after its appearance in Panama in the 
previous September, suggest that a simple 
country-to-country spread is not a satisfac- 
tory explanation. 

By the end of 1991, when the Latin Ameri- 
can epidemic had been in progress for about 
eleven months, a total of 299,332 cases and 
3,993 deaths had been reported from four- 
teen countries in Central America and South 
America. Of them, 77 percent of the cases 
and 72 percent of the deaths occurred in 
Peru. By the end of 1994, some 963,171 cases 
and 9,552 deaths were reported from twenty 
of the twenty-one countries of Central 
America and South America (only Uruguay 
was spared). Of the four-year totals, 57 per- 
cent of the cases and 46 percent of the deaths 
were reported from Peru. The overall case- 
fatality rate for the entire Latin American 
experience during the first four years of the 
epidemic was 0.99 percent, a remarkably 
low figure for which the deliverers of health 
care in all of the Latin American countries 
should be congratulated. 

In order to understand the epidemiology 
of cholera in Latin America, it is important 
to estimate the force of infection throughout 
the entire area. That force would determine 
the magnitude of conversion from immu- 
nologically susceptible to resistant individu- 
als in the population. In order to 
determinate that force, an estimate of the 
frequency of inapparent and mild unre- 
ported infection is needed. (Until then, one 



John P. Craig 31 



Mean Case-Fatality Ratio (%) 



Fig. 3. Mean 
annual attack rates 
(solid bars) and 
mean case fatality 
ratios (open bars) 
in Central and 
South American 
countries, 1991- 
1994. Countries are 
listed in order of 
their mean annual 
attack rates for the 
four-year period. 





) 1 


2 3 

. I .... I . 


4 


) 6 


7 a 


9 1 
















" 










Guatemala 
El Salvador 


S± 


Bolivia 






Nicaragua 






Belize 




™ 


Panama 




™ 






Colombia 
Brazil 


i 3 




Guyana 






Mexico 
French Guiana 






Venezuela 










Argentina 






Surinam 
Costa Rica 






















Chile 

Paraguay 

























200 300 400 500 

Mean Annual Attack Rate/100.000 



can only extrapolate from earlier studies in 
other parts of the world.) Studies based on 
postepidemic serologic surveys have pro- 
duced estimates of infection /case ratios as 
high as 100:1. 12 Estimates based on stool cul- 
tures in family and community contacts 
yielded ratios as low as 3:1. If the geometric 
mean of 17:1 is applied to the South Ameri- 
can data, we see that in 1991 alone in Peru, 
about 3,900,000 persons — or 17 percent of 
the entire population of the country — were 
probably infected; by 1994, 9.3 million, or 40 
percent, had been infected. 

Although those are probably rough un- 
derestimations, we can be assured that large 
segments of the Latin American population 
have been and will be infected in succeeding 
years, and that regardless of the infec- 
tion/case ratios that prevailed in the epi- 
demic, the number of people infected and 
immunized far exceeded the reported cases. 
It can be assumed that those infected were 
rendered more resistant to reinfection than 
the previously uninfected members of their 
communities. That herd immunity will be a 
major factor in determining the incidence 
and age distribution of cholera in Latin 
America in the years to come. The other 



major factor will be the availability of vibrios 
in the environment for infection of the bio- 
logically and immunologically susceptible 
members of the community. 

Figure 3 shows the average annual mor- 
bidity rates for the first four years of the 
Latin American epidemic in all of the coun- 
tries affected. On the same graph the aver- 
age case-fatality rates are shown. It is 
certainly recognized that those political 
units do not reflect the natural ecologic fea- 
tures that probably serve as the major deter- 
minants in the spread of disease. 
Unfortunately, population and disease data 
for such biomes are not available. Country 
and provincial data are all that exist, and 
they are useful for a rough tracking of the 
course of dissemination. Nevertheless, 
countries with very large areas — including 
Mexico, Brazil, and Argentina — all had low 
overall attack rates that did not accurately 
reflect the higher rates that occurred in re- 
stricted parts of their respective territories. 

By March of 1993, a little over two years 
after the first cases were recognized in Peru, 
all countries of Central America and South 
America except Uruguay had been seeded. 
The South American countries followed a 
roughly centrifugal pattern of spread from 
the initial major focus in Peru. The Central 
American spread was roughly linear from 
Southern Mexico toward Panama. The first 
cases appeared in Venezuela, Argentina, 
and Surinam in the end of 1991 or in the early 
months of 1992. Guyana, French Guiana, 
and Paraguay did not experience their first 
cases until nearly a year later. No cases were 
reported from the island nations of the Car- 
ibbean throughout the first four years of the 
epidemic. That would suggest that all intro- 
ductions were from the Pacific shores of the 
continent, regardless of the nature of the 
source. 



32 Cholera 



The generally low case-fatality rates were 
a striking feature of the entire American ex- 
perience with cholera. Figure 3 clearly 
shows that all of the countries that had 
higher morhidity rates enjoyed remarkably 
low case-fatality rates. In Peru, with an av- 
erage annual morbidity rate of 580/100,000, 
the average case-fatality rate was about 0.8 
percent. Those values were repeatedly con- 
firmed by outside observers, attesting to the 
excellent clinical management of cases in the 
face of overwhelming caseloads, especially 
in the first year of the epidemic. The high 
case-fatality rate for Surinam is of little sig- 
nificance since the total number of cases was 
only twelve. 

In order to examine in more detail the true 
nature of the progression and seasonal dis- 
tribution throughout the four-year period, 
monthly morbidity rates (cases/ 100,000 
population /month) were calculated for ten 
selected countries, five in South America 
and five in Central America. The data are 
shown in Figure 4. In each country the sea- 
sonal peaks tended to occur in the same part 
of the year each year. During the forty-eight 
months of 1991-1994, it was possible to iden- 
tify fifty-two distinct seasonal peaks in sev- 
enteen of the countries involved. When 
those countries were further divided into 
two groups according to latitude, it turned 
out that in the twelve countries whose land- 
mass lies predominantly north of the equa- 
tor, most of the peaks occurred between 
January and June. In the six countries lying 
predominantly south of the equator, most of 
the peaks occurred between July and De- 
cember. Those data are depicted in Figure 5. 
The tendency can also be seen in Figure 4. In 
the five South American countries, peaks 
occurred predominantly in the early part of 
each year. In the five Central American 
countries, peaks occurred predominantly in 



the latter half of the year. The incidence data 
shown in Figure 4, combined with this dif- 
ference in seasonal predominance, suggest 
that environmental factors related to hours 
of sunlight and perhaps associated tempera- 
ture and climatic factors played an impor- 
tant role in determining the timing of the 
annual peaks. In other words, during the 
first four years of that neotropical epi- 
demic — regardless of the month of introduc- 
tion into each country — the seasonal cycles 
tended to settle into a cyclic pattern of late- 
summer and fall epidemics even though the 
vast bulk of the epidemic occurred in popu- 
lations living between the Tropics of Cancer 
and Capricorn where temperature extremes 
do not occur. In fact, most disease occurred 
between the 15 N and 15 S latitudes, where 
seasonal temperature differences are even 
less pronounced. 

These observations tend to support the 
notion that after the initial introduction of 
vibrios into a region, intrinsic environ- 
mental factors played the most influential 
role in determining seasonal fluctuations in 
the available numbers of infectious vibrios 
in the environment and hence the number of 
cases. Herd immunity and sanitary meas- 
ures probably influenced the magnitude of 
those peaks to some extent but not their 
distribution in time and place. If immunity 
and human intervention were the major 
epidemiologic determinants of incidence, 
one should expect a gradual fall in incidence 
through all seasons after an initial single 
epidemic peak. The data depicted in Figure 
4 suggest, on the other hand, a tendency 
toward diminishing annual peaks following 
a maximum first-year peak. Such a pattern 
occurred in seven of the ten countries shown 
in Figure 4. 

A more detailed examination of the an- 
nual outbreaks in Chile is instructive. Because 



John P. Craig 33 



Monthly Cholera Attack Rates in Ten Countries 

1991-1994 




c 
o 



o 
o 
o_ 

o" 

o 

"55 
o 

(0 

O 




02- 
0.15- 

0.1 • 

0.05- 

0- 



I 



as 



Chile 



150 
120 -i 

90 
60 H 
30 





25- 
20- 



15 — 



10- 
5^ 



E! Salvador 



Belize 



^ 




1991 



1992 



1993 



1994 





Nicaragua 


j 


; 




. Jl* 


\ 


i^L 



1991 



1992 



1993 



1994 



Fig. 4. Monthly cholera morbidity rates (cases/100, 000/month) in ten selected countries during the first four 
years of the cholera epidemic in Central and South America. 



34 Cholera 



of the low incidence there and perhaps be- 
cause of better conditions of environmental 
hygiene, the overall incidence during the 
four years of observation was very low. Yet 
the disease appeared in a series of very well 
separated sharp autumn peaks separated by 
periods in which no disease was reported. 
The first reports were in mid-April in 1991, 
and the outbreak ended by mid-May of that 
year. In all, forty cases were reported. Chol- 
era then seems to have disappeared entirely 
until January of 1992, in the Chilean mid- 
summer, when a six-month outbreak com- 
prising seventy-one cases occurred with a 
peak in February, March, and April. The 
disease again disappeared until January 
1993, when another small outbreak of 
twenty-nine cases again occurred between 
January and May of that year. In 1994 only 
one case was reported in late December. 
Thus, three distinct prolonged periods of 
several months during which cholera seems 
to have disappeared were punctuated by 
four separate small outbreaks. 

Was cholera reintroduced into northern 
Chile on four separate occasions, or did the 
temporal distribution suggest an environ- 
mental reservoir, perhaps in association 
with the microflora or fauna of local fresh- 
water bodies that was reactivated in some 
manner during the warmer months of each 
year? Perhaps, in order to disclose the man- 
ner in which pathogenic strains of Vibrio 
cholerae can be maintained in the nonhuman 
environment, it would be wise to examine 
more carefully such areas as Chile in which 
a year-round human-to-human passage of 
cholera vibrios cannot be sustained because 
of a relatively high level of personal and 
community sanitation. 

There have been a number of unexplained 
events in the history of cholera that are 
bound to raise the antennae of the curious. 



One of those has been the uncanny tendency 
of disease incidence to rise simultaneously 
in distant and apparently unconnected re- 
gions of the globe. That was again demon- 
strated when ten African nations reported 
over 45,000 cases with 3,488 deaths during 
the first six months of 1991, the year in which 
the South American epidemic began and in 
which the population suffered its highest 
incidence. 13 Cholera had become perma- 
nently endemic in much of central Africa in 
the early 1970s; in the next two decades it can 
be assumed that much of the African popu- 
lation had been immunized by inapparent 
or manifest infection. Yet, for unexplained 
reasons, the same population (of course, 
augmented annually by immunologically- 
naive newborns) experienced a marked in- 
crease in incidence and mortality during the 
same six months that the Latin American 
epidemic took its greatest toll. The strains of 
Vibrio cholerae responsible for the two epi- 
demics were different. 

Are there global climatic or other environ- 
mental influences at work that significantly 
alter the numbers of infectious organisms 
available for consumption by the human 
populations in different parts of the globe at 
the same time? Another riveting fact was 
strikingly demonstrated by the concurrence 
of those two equatorially-centered epidem- 
ics. In spite of the two decades of endemic 
cholera that much of central Africa had ex- 
perienced between 1970 and 1990, case-fa- 
tality rates in African countries ranged from 
6 percent to as high as 30 percent in the great 
flurry of cholera activity in 1991. In South 
America, on the other hand, where the 
population had not experienced the immu- 
nizing effects of two decades of endemic 
cholera, case-fatality rates ranged from 1 
percent to 2 percent, with countries suffer- 
ing the highest morbidity rates enjoying the 



John P. Craig 35 




Fig. 5. Distribution of epidemic peaks by month in eighteen countries according to latitude. Solid bars indicate 
south; open bars indicate north. 



lowest mortality. Can all of the difference in 
disease outcome be attributed to superior 
management of cases by the health care de- 
liverers of South America and Central 
America? Had the case-fatality ratios been 
reversed, might we not have been tempted 
to attribute the difference to longer experi- 
ence in treating severe cholera, possibly in 
concert with a higher level of herd immu- 
nity? We are left without satisfactory 
answers. 

Throughout medical history, the ten- 
dency to discover the source of particularly 
loathsome and feared disease in a foreign 
and unfamiliar nation has always been with 
us. The French pox, the Spanish influenza, 
and Asiatic cholera come to mind. When the 
first case of cholera in the United States in 



the Seventh Pandemic occurred in Texas in 
1973, assumptions of introduction by Viet- 
namese immigrants were immediately 
voiced. Modern techniques of strain identi- 
fication rapidly disabused us of that notion 
and demonstrated that the organism re- 
sponsible for that case was an indigenous 
strain of Vibrio clwlerae that resides as a mem- 
ber of the autochthonous flora of United 
States Gulf Coast estuarine waters, and that 
it could be readily distinguished from Asian 
strains and from the strains responsible for 
the recent Latin American epidemic. 14 
Moreover, it was shown that those 
autochthonous strains enjoyed a special as- 
sociation with shellfish and large and small 
Crustacea, upon which they can achieve 
much larger populations than in open water 



36 Cholera 



because of their peculiar use of certain en- 
zymes that allow them to profit from their 
propinquity with those animal hosts. Does 
the current Latin American epidemic pro- 
vide us with any evidence for or against the 
proposition that it, too, could have resulted 
from the activation of a hitherto dormant 
population of pathogenic vibrios in this 
hemisphere rather than an importation from 
China? I believe that at the present time the 
question cannot be answered. But the evi- 
dence suggests that multiple introductions 
occurred along the Pacific Coasts of Central 
America and South America, from Mexico 
to Peru, and that those introductions could 
at least as readily have been achieved 
through the amplification of vibrios on an 
algal bloom as from a single or multiple 
introductions from bilge from an Asian 
freighter. We must keep an open mind in 
order to arrive at an answer to the remaining 
and most perplexing problem in cholera bi- 
ology. 

A Natural Home 

A major innovation in thinking about the 
natural history of cholera arose just prior to 
the onset of the current Seventh Pandemic. 
For the first time, serious questions were 
asked about the long-held notion that the 
human small bowel is the natural reservoir 
of the cholera vibrio, the major locus in na- 
ture where the microorganism persists. The 
conventional notion that had prevailed since 
Robert Koch discovered the cholera vibrio in 
the ileal mucosa of patients who had died of 
the disease, required either an endless hu- 
man chain of transmission or a prolonged, 
silent carrier state similar to the decades- 
long carrier state in the gallbladder of Salmo- 
nella typhi carriers. Otherwise, how could 
one explain the repeated disappearances 
and recrudescences after many disease-free 



months or years? But tireless efforts to dem- 
onstrate such carriers in cholera had failed. 
Credit must be given to T. Aiden Cock- 
burn and James G. Cassanos for being 
among the first'to systematically study envi- 
ronmental factors that might account for the 
striking seasonal variations noted in en- 
demic cholera in Bengal, a major residuum 
of the disease in the interepidemic period 
preceding the onset of the Seventh Pan- 
demic. 15 They postulated that the reason for 
perennial persistence of the disease in Ben- 
gal was not the persistence of infection in the 
urban population of Calcutta but rather the 
persistence of cholera vibrios in village wa- 
terponds (tanks) in rural Bengal. The es- 
sence of their thinking is best revealed in the 
following quotation: 

We suggest that in Bengal the endemic infec- 
tion is primarily rural, and that the Calcutta 
urban region is of secondary importance. 
Many other cities in the world with large 
populations and overcrowding like Calcutta 
have experienced cholera epidemics, but in 
these always the infection has died out. Lon- 
don in the mid-l'Hh centurv days of John Snow 
closely resembled Calcutta with its masses of 
people, insanitary slums, and cholera-infected 
river, but the vibrio failed to establish a perma- 
nent foothold. Calcutta has what the other cit- 
ies do not have, a surrounding countryside in 
which cholera always exists. 10 

Those studies demonstrated a clear corre- 
lation between the incidence of cholera in 
rural villages, and sunlight and pH in village 
ponds, suggesting that the ponds were the 
chief reservoir and means of spread of the 
vibrio. They proposed that in hot, dry 
weather algae in the ponds raised the pH to 
high levels that afford cholera vibrios a se- 
lective advantage over other organisms. The 
implication is that cholera vibrios are capable 
of surviving indefinitely outside the human 



John P. Craig 37 



host in an appropriate nonhuman environ- 
mental niche, although Cockburn and Cas- 
sanos did not say so explicitly. Nor did they 
explicitly postulate the amplification of vi- 
brio populations on the surface of or in inti- 
mate association with algae, but rather they 
implied that the vibrios were free-swim- 
ming autochthonous members of the pond 
flora and that vibrio populations rose and 
fell with pH changes. 

More recently Sirajul Islam and David 
Bradley and their colleagues, after conduct- 
ing studies in ponds in Bangladesh in the 
same areas studied by Cockburn and Cas- 
sanos three decades earlier, have proposed 
an even more central and crucial role for 
blue-green algae (Cyanobacteria) in the ecol- 
ogy of cholera. 17 They hypothesized that 
cholera vibrios survive inside the nutrient- 
rich mucilaginous sheath of blue-green al- 
gae for long periods of time, where they 
enjoy a symbiotic relationship in perpetuity. 
Rapid amplification of vibrio populations 
occurs during algal blooms followed by re- 
lease from the mucilaginous sheath during 
reproduction and disintegration of algal 
cells. They postulated that the internal mul- 
tiplication within the mucilaginous algal 
sheath may explain previous failures to re- 
cover cholera vibrios from water samples 
that have been rendered plankton-free be- 
fore culture. The authors further proposed 
that the salinity requirements of Vibrio chol- 
erae can be reduced when they find them- 
selves inside the highly specialized 
environment of the mucilaginous algal 
sheath. That might help to explain how the 
distribution of cholera vibrios can some- 
times be extended to freshwater environ- 
ments instead of being restricted to 
estuarine waters. 

Meanwhile, another challenge to the "ul- 
timate human reservoir" concept in cholera 



epidemiology was led mainly by Rita Col- 
well and her many colleagues and students 
at the University of Maryland. Their work 
arose from a background of studies on the 
ecology of Vibrio parahaemolyticus in 
Chesapeake Bay, where they discovered 
that organism (and later Vibrio cholerae) was 
capable of first colonizing the exoskeletons 
of copepods and then "hibernating" in a 
nonculturable but viable state for long peri- 
ods. Colwell postulated that Vibrio cholerae is 
an autochthonous inhabitant of moderately 
saline, estuarine waters in several reservoir 
zones of the world in which they can remain 
in a dormant state for many years. In the 
dormant state, the vibrios are greatly re- 
duced in size and can be cultivated only 
under special conditions. 18 The seemingly 
oxymoronic appelation of "nonculturable 
but viable" organisms has created bewilder- 
ment in some quarters, but now that the 
terms of reference have been established 
and reasonably defined, the concept has be- 
come a valuable and important contribution 
to our understanding of vibrio ecology. 

Thus, many of the epidemiological ques- 
tions raised by the current epidemic in Cen- 
tral America and South America had 
already been addressed by several groups of 
investigators. The advent of widespread dis- 
semination in a "new" continent has pro- 
vided fresh opportunities to define the 
natural history of the cholera vibrio and to 
determine its "natural home." Until the 
natural habitat(s) of the microbe can be fully 
defined — both qualitatively and quantita- 
tively — the natural history of cholera will 
remain clouded in mystery. 

An Immune Evasion 

Another event in the saga of cholera oc- 
curred in late 1992, when a disease that was 
clinically indistinguishable from typical 



38 Cholera 



cholera appeared in India and Bangladesh. 
Laboratory technicians accustomed to the 
serological identification of cholera vibrios 
by agglutination with antisera immediately 
recognized that although the organisms iso- 
lated from patients in the outbreak had all 
the expected properties of cholera vibrios, 
they failed to agglutinate with the standard 
anti-Ol sera. 19 

Ever since the agglutinating system was 
devised, all cholera vibrios causing epi- 
demic disease had belonged to a single sero- 
group that was arbitrarily assigned the 
number "1." Because the antigen involved is 
a surface, or O, antigen on the bacterial cell 
wall, the serogroup of all epidemic and pan- 
demic cholera strains thus far isolated had 
been designated "Ol." In the intervening 
years, 138 O antigens had been discovered, 
and all of the strains from 02 to 0138 had 
been considered "non-Ol" Vibrio cholerae. If 
they occasionally caused disease, it was al- 
ways sporadic, usually occurred in small, 
nonspreading outbreaks, and never dis- 
played the character of "dispersiveness" 
that was the major, ineffable but critical 
property of the epidemic Ol strains. 20 Be- 
cause the organism causing the outbreak on 
the shores of the Bay of Bengal in December 
1992 possessed a hitherto unknown surface 
antigen, it was given the moniker Bengal 
0139. 

Earlier studies had clearly shown that a 
number of the non-Ol strains of Vibrio chol- 
erae that had been isolated from the environ- 
ment and from occasional patients and small 
outbreaks of diarrhea throughout the Sev- 
enth Pandemic could occasionally produce 
the same enterotoxin molecule as did the Ol 
strains. 21 Therefore, in retrospect, it should 
not have been surprising that some day one 
of those toxinogenic strains bearing a new or 
different somatic or surface lipopolysaccha- 



ride (specifically, the 0139 antigen) could 
somehow acquire that elusive property of 
dispersiveness, sometimes referred to as 
epidemic potential, that apparently was not 
possessed by any of the previously known 
non-Ol strains. Bengal 0139 appeared to be 
just such a strain. 

Bengal 0139 spread rapidly throughout 
most of India, Bangladesh, Pakistan, Sri 
Lanka, Nepal, Afghanistan, Thailand, 
China, and Malaysia. Imported cases were 
reported in Europe and the United States, 
but there was no local spread. Its distribu- 
tion in the populations it infected confirmed 
the suspicions of many of those who had 
worked for decades on the immunology of 
cholera — that acquired immunity depended 
largely on the antibodies directed against 
the major somatic antigens rather than on 
antitoxic immunity. When Bengal 0139 en- 
tered communities in India and Bangladesh 
that had experienced endemic Ol cholera 
for decades, it behaved like a new disease; 
most cases were found in adults, just as had 
been true of Ol cholera in Latin America in 
1991. Since the enterotoxins of Ol and 0139 
are identical, the difference in age distribu- 
tion suggests that the preexisting antitoxic 
immunity engendered by long-standing en- 
demic Ol cholera offered no protection. One 
could anticipate that if 0139 becomes per- 
manently endemic in the Indian subconti- 
nent it will gradually shift to a childhood 
disease as Ol cholera has done. 

Conclusion 

The Seventh Pandemic has brought about 
a much greater understanding of the way 
that the bacterium known as Vibrio cholerae 
can produce disease in the individual hu- 
man being. We have learned rather success- 
fully how to treat patients who are its 
victims. Our knowledge of immunity is still 



John P. Craig 39 



insufficient to produce a really effective 
vaccine, however. We are just beginning to 
understand the complex ecology of the bac- 
terium, and we are slowly but surely mov- 
ing toward the realization that its 
tempestuous encounters with our species 
may be a rather incidental — even inconse- 
quential — part of its life history in the grand 
scheme of things. 

In our anthropocentric view, this notion 
may be difficult to accept, but it is likely to 
be true. Its real home is more likely to be 
upon and within a variety of marine, estu- 
arine, or even freshwater small plants, ani- 
mals, and other bacteria. The remote and 
ancient origins of its virulence factors, and 
their unique affiliation with the human spe- 
cies, remain a profound mystery. Even more 
remote from our understanding is the physi- 
cal basis for that quintessential property of 
those special clones of the organism that 
render them capable of rapid spread 
through a human population, namely the 
property of dispersiveness. 

What, then, is the outlook for cholera in 
the twenty-first century? The enlightenment 
and experience we have gained during the 
first thirty-four years of the Seventh Cholera 
Pandemic make it clear that the most effec- 
tive means of reducing the effects of chol- 
era's ravages are twofold: (1) increase the 
availability of clean water protected from 
fecal contamination in countries where 
these amenities do not yet exist; and (2) con- 
tinue relentlessly to improve and sustain the 
training of health professionals in the proper 
use of both oral and parenteral water and 
electrolyte replacement therapy for all kinds 
of diarrhea. A keen level of alertness and 
action in both of those areas has the added 
virtue of reducing morbidity and mortality 
from all infectious diarrheal diseases, not 
just cholera. Moreover, safe and dependable 



water represents one of the major hallmarks 
of civilization that will enhance the quality 
of life for all. Fear of cholera spearheaded the 
nineteenth-century movements that estab- 
lished boards of health and sanitary codes in 
the societies we now call "developed." Let 
the process continue apace at the highest 
priority in the next century. Unfortunately, 
the miserably low rate of progress in this 
area in the poor countries of the world in the 
last half-century gives one little reason for 
optimism that improvements will be suffi- 
cient to avert continuing outbreaks of chol- 
era in the decades to come. The incidence in 
Asia, Africa, and South America will be in- 
versely related to the success these countries 
have in providing clean water and food to 
their citizens. 

Better understanding of the immune 
mechanisms by which recovered victims of 
cholera are rendered resistent to reinfection 
will almost certainly lead to the develop- 
ment of an effective vaccine within the next 
decade. It would be naive, however, to ex- 
pect, regardless of the success of such a vac- 
cine in protecting the individual, that 
vaccine delivery systems will be able to sus- 
tain the massive and perpetual worldwide 
immunization programs that would be nec- 
essary to control or prevent a disease caused 
by an organism that cannot realistically be 
eradicated from a permanent, natural, non- 
human environment reservoir. We already 
know that cholera is robbed of its dispersive 
power when it enters communities that pro- 
vide clean water and some means of inter- 
rupting the fecal-oral transmission chain. 
During the past three decades, cholera has 
utterly failed to spread in the United States, 
Japan, Australia, and western Europe in 
spite of repeated introductions, and a per- 
manent, autochthonous estuarine reservoir 
along the gulf coast of the United States. 



40 Cholera 



We also already know that good treat- 
ment leads to 99 percent recovery. The pri- 
orities, therefore, should be clear. An 
acceptable level of cholera control can 
clearly be achieved and maintained without 
eradication of the causative bacterium from 
the planet and without universal vaccina- 
tion, if societies have the will to provide for 
these basic necessities. 



Notes 



1. John Snow, On the Mode of Communication of 
Cholera, 2nd ed. (London: Churchill, 1855; reprinted, 
New York: Commonwealth Fund, 1936). 

2. R. Koch, "Die Conferenz zur Erorterung der 
Cholerafrage," Deutsche medizinische Wochenschrift 
10 (1884): 499. 

3. Koch's Postulates as translated in G. S. Wilson 
and A. A. Miles, Topley and Wilson's Principles of 
Bacteriology, Virology, and Immunity, 6th ed., 2 vols. 
(Baltimore: Williams and Wilkins Company, 1975). 
The three postulates are: (1) The microorganism 
should be found in all cases of the disease in ques- 
tion, and its distribution in the body should be in 
accordance with the lesions observed; (2) The micro- 
organism should be cultivated outside the body of 
the host, in pure culture, for several generations; and 
(3) The organism so isolated should reproduce the 
disease in other susceptible animals. 

4. R. B. Hornick, S. I. Music, R. Wenzel, R. Cash, 
J. P. Libonati, M. J. Snyder, and T. E. Woodward, 
"The Broad Street Pump Revisited. Response of Vol- 
unteers to Ingested Cholera Vibrios," Bulletin of the 
New York Academy of Medicine 47 (1971): 1181-91. 

5. J. P. Craig, "the Enterotoxic Enteropathies," 
Symposia of the Society for General Microbiology 22 
(1972): 129-55; J. P. Craig, "A Survey of the Entero- 
toxic Enteropathies: hi Cholera and Related Diar- 
rheas," 43rd Nobel Symposium ... 2 97S (Basel: Karger, 
1980), 15-25; J. P. Craig, "The Vibrio Diseases in 
1982: An Overview," in Bacterial Diarrheal Diseases, 
ed. Y. Takeda and T. Miwatani (Tokyo: KTK Scien- 
tific Publishers, 1985), 11-23; J. P. Craig, "The Search 
for the Cause of Cholera Since Robert Koch's Discov- 
ery of the Kommabacillus," in Vibrio cholerae and 
Cholera, ed. Y. Takeda and S. Kuwahara (Tokyo: KTK 
Scientific Publishers, 1988), 33-45; J. B. Kaper, J. G. 
Morris, Jr., and M. M. Levine, "Cholera," Clinical 



Microbiology Reviews 8 (1995): 48-86. 

6. S. N. De, "Enterotoxicity of Bacteria-free Cul- 
ture Filtrate of Vibrio cholerae," Nature 183 (1959): 
1533. 

7. A. M. Kamal, "The Seventh Pandemic of 
Cholera," in Cholera, ed. D. Barua and W. Burrows 
(Philadelphia: W. B. Saunders, 1974), 1-14. 

8. F. Chen, G. M. Evins, W. L. Cook, R. Almeida, 
N. Hargrett-Bean, and K. Wachsmuth, "Genetic Di- 
versity among Toxigenic and Nontoxigenic Vibrio 
cholerae Ol Isolated from the Western Hemisphere," 
Epidemiology and Infection 107 (1991): 225-33. 

9. R. Pollitzer, Cholera, WHO Monograph Series 
No. 43 (Geneva, 1959), 1019. 

10. World Health Organization, Weekly 
Epidemiological Record (Geneva). 

11. C. Anderson, "Cholera Epidemic Traced to 
Risk Miscalculation," Nature 354 (1991): 255 

1 2. C. B. Gerichter, I, Sechter, J. Cohen, and A. M. 
Davies, "A Serological Survey for Cholera Antibod- 
ies in the Population of Jerusalem and Surround- 
ings," Israel journal of Medical Science 9 (1973): 980. 

13. WHO Press, World Health Organization, Of- 
fice of Information, Geneva, Press Release WHO/ 64, 
Dec. 30, 1991. 

14. Chen et al., "Genetic Diversity." 

15. T. A. Cockburn and J. G. Cassanos, 
"Epidemiology of Endemic Cholera," Public Health 
Refiorts 75 (1960): 791-803. 

16. Ibid. 

17. M. S. Islam, B. S. Drasar, and D. J. Bradley, 
"Long-term Persistence of Toxigenic Vibrio cholerae 
Ol in the Mucilaginous Sheath of a Blue-Green Alga, 
Anabaena variabilis," Journal of Tropical Medicine and 
Hygiene 93 (1990): 133-39; M. S. Islam, B. S. Drasar, 
and R. B. Sack, "Probable Role of Blue-green Algae 
in Maintaining Endemicitv and Seasonality of Chol- 
era in Bangladesh: A Hypothesis," Journal of Diar- 
rheal Disease Research 12(1994): 245-56. 

18. R. R. Colwell, J. Kaper, and S. W. Joseph, 
"Vibrio cholerae, Vibrio parahemolyticus and Other 
Vibrios: Occurrence and Distribution in Chesapeake 
Bay," Science 198 (1977): 394-96; A. Huq, R. R Col- 
well, R. Rahman, A. Ali, M. A. R. Chowdhury, S. 
Parveen, D. A. Sack, and E. Russek-Cohen, "Detec- 
tion of Vibrio cholerae Ol in the Aquatic Environment 
by Flourescent-Monoclonal Antibody and Culture 
Methods," Applied Environmental Microbiology 56 
(1990): 2370-73; R. R. Colwell and W. M. Spira" "The 
Ecology of Vibrio cholerae," in Cholera, ed. D. Barua 
and W. B. Greenough HI (New York: Plenum Pub- 
lishing Corporation, 1992), 107-27; R. R. Colwell and 
A. Huq, "Vibrios in the Environment: Viable But 
Nonculturable Vibrio cholerae," in Vibrio cholerae and 
Cholera: Molecular to Global Perspectives, ed. I. K. 
Wachsmuth, P. A. Blake, and O Olsvik (Washing- 
ton, D.C: ASM Press, 1994), 117-133. 

19. Cholera Working Group, International Cen- 
tre for Diarrhoeal Diseases Research, Bangladesh, 
"Large Epidemic of Cholera-like Disease in Bangla- 
desh Caused by Vibrio clwlerae 0139 Synonym Ben- 
gal," Lancet 342 (1993): 387-90; World' Health 
Organization, Weekly Epidemiological Record. 



John P. Craig 41 



20. The term "dispersiveness" as applied to the 
quintessential feature of epidemic cholera seems to 
have been introduced by Major Greenwood in his 
chapter on cholera in Epidemics and Crowd Diseases 
(London: Williams and Norgate, Ltd., 1935), 165. No 
better word has been proposed. It is not completely 
clear whether he borrowed the word from a German 
equivalent used by the German epidemiologist 
Sticker or introduced it himself. Greenwood's words 
of 1935 are particularly apt: "Cases of cholera in its 
deadly form were accurately described in the Hip- 
pocratic collection; epidemics of cholera occurred, 
for instance, in Alkmar in 1548, in Nimes in 1645, in 
London in 1669 and 1676, in Vienna in 1786, before 
the nineteenth century. But epidemiologists agree- 
ing in little else agree that the particular manifesta- 
tions of cholera which showed themselves in Europe 
after Waterloo differed epidemiologically from any- 
thing which had been seen before. This difference 
may be summarized in a phrase as a difference in 
dispersiveness. 'What,' writes Sticker, 'was new in 
the history of Indian cholera [he is writing about the 
events of 1817] and rightly caused apprehension 
there as well as here was the further intelligence that 
this destructive epidemic no longer confined itself 
to a particular area and at the accustomed season of 
the year appeared simultaneously in several places, 
but set itself in motion, under the influence of some 
mysterious impulse began to travel, and, without 
paying attention to the season of the year, attaching 
itself to the lines of human intercourse, spread 
widely in various directions, exacting everywhere 
hecatombs of victims.'" For those interested in a 
provocative discussion of the epidemiology of chol- 
era before the Seventh Pandemic, Greenwood's 
chapter will prove rewarding. 

21. J. P. Craig, K. Yamamoto, Y. Takeda, and T. 
Miwatani, "Production of Cholera-like Enterotoxin 
by a Vibrio cholerae non-Ol Strain Isolated from the 
Environment," Infection and Immunity 34 (1981): 90- 
97. 



JOHN P. CRAIG is Distinguished Teaching Professor 
Emeritus of Microbiology and Immunology at the State 
University of New York Health Science Center at 
Brooklyn. He has been Chairman of the U.S. Cholera 
Panel, U.S.-Japan Cooperative Medical Sciences 
Program; member of the Cholera Advisory Committee, 
National Institute of Allergy and Infectious Diseases, 
National Institutes of Health; and Chairman of the 
Scientific Working Group, Bacterial Enteric Infections, 
Programme for Control of Diarrhoeal Diseases, World 
Health Organization. He was a member of the staff of 
the former Pakistan-SEATO Cholera Research 
Laboratory in Dhaka, Bangladesh. 



ACKNOWLEDGMENTS 

The author wishes to express his deep thanks to Dr. 

Haseeb Siddiqi for his many suggestions and 

assistance in the preparation of the figures and the 

map and for his invaluable help in reviewing the 

manuscript. 



42 Cholera 



The Tuberculosis Story: From Koch 
to the Year 2000 



Mahfouz H. Zaki and Mary E. Hibberd 



For decades, tuberculosis mortality and 
morbidity in most countries had been 
declining even before the recognition of the 
tubercle bacillus by Robert Koch in 1882. 
That decline was attributed in part to a con- 
comitant improvement in the environ- 
mental-socioeconomic-sanitary complex 
and to a gradual reduction in the infection 
reservoir. 

In 1941 Louis Dublin of the Metropolitan 
Life Insurance Company predicted that tu- 
berculosis would be eradicated by I960. 1 
"No Tuberculosis by 1960" was the slogan 
of the National Tuberculosis Association for 
decades to come. With the introduction of 
streptomycin in 1948 and isoniazid and 
para-aminosalicylic acid in 1952, many pub- 
lic health and preventive medicine experts 
predicted the eventual elimination of tuber- 
culosis as a public health problem within a 
decade or two. In 1958 James Perkins issued 
a serious challenge for a "formal concen- 
trated program of eradication of tuberculo- 
sis from the whole face of the earth." 2 The 
following year, the Arden House Confer- 
ence on Tuberculosis in Harriman, New 
York, considered the eradication of tubercu- 
losis a prime objective. 3 

Literally, eradication of an infection 
means the wiping out of the infection and 
the extinction of the responsible pathogen. 
As the name implies, eradication is an abso- 



lute process and not a relative goal. In other 
words, it follows an "all-or-none" phenome- 
non. Mathematically, an infection will reach 
the baseline if the regression slope of the 
trend remains negative on successive years. 
The rapidity with which the infection will be 
eradicated depends upon the magnitude of 
the regression slope. 

A question frequently asked about public 
health is: Has any disease actually been radi- 
cally eradicated? In principle, is it possible 
to reduce an infection to the degree of extinc- 
tion or eradication? Theoretically speaking, 
the answer is yes. Certain prerequisites, 
however, have to be met. The disease should 
have no carrier state or animal reservoir, 
should be easily diagnosed, and should 
have easily deployable prophylactic tools 
available. Very few diseases can satisfy such 
criteria, with the notable exceptions of 
smallpox and measles. 

Experience gleaned from many infectious 
diseases has shown that once the morbidity 
of a disease reaches a very low level, a resid- 
ual infection usually persists in the popula- 
tion and a state of equilibrium becomes 
established between the agent, host, and en- 
vironmental components of the disease 
process. Although malaria eradication pro- 
grams have been carried out in many parts 
of the world for more than six decades, ma- 
laria cases are still reported sporadically in 



CADUEUS ♦ Spring 1996 



Vol. 12. No. 1 



the so-called eradicated areas. Some of those 
cases are imported, while others are indige- 
nous. 

The United States and the Scandinavian 
countries started extensive eradication pro- 
grams for bovine tuberculosis in the late 
1930s and early 1940s. Slaughtering of in- 
fected cattle was an essential feature of the 
program, but — in spite of that draconian 
measure — bacteriologic eradication was not 
achieved. The disease did, however, reach a 
very low level, which has been static for 
several years and may remain so for decades 
to come. F. L. Soper, in his superb discussion 
of the problems encountered in the 
epidemiology of a disappearing or retreat- 
ing disease, refers to the hidden foci of infec- 
tion, the unrecognized methods of 
transmission, and the erratic behavior of re- 
sidual infections — all of which present real 
problems in the eradication process. 4 

Some investigators, realizing the diffi- 
culty of achieving bacteriologic eradication, 
prefer to use the phrase "eradication as a 
public health problem," which denotes 
nothing but substantial control. Omitting 
the problem of semantics and assuming a 
more realistic attitude (thus substituting 
control for eradication), let us review in brief 
where we stand in the control of tuberculo- 
sis, as well as the far-fetched goal of elimina- 
tion. The indices that describe the 
experience of a population with tuberculosis 
are the mortality rates, the morbidity rates, 
and the prevalence of tuberculous infection 
in the community. 

Mortality Rates 

For most infectious diseases, including 
tuberculosis, mortality statistics have been 
considered relatively reliable measures for 
international comparisons. Such compari- 
sons are doubtless subject to many sources 



of error, particularly the extent of complete- 
ness of reporting and the criteria used to 
define a tuberculosis death. The well-known 
pattern of tuberculosis mortality among 
males recognized in the early decades of this 
century was characterized by relatively high 
mortality among children under the age of 
four years, followed by a very low rate in the 
age group between five and fourteen years. 
The rate gradually rose to a peak between 
twenty-four and thirty-six years, followed 
by a plateau or slight decline until the age of 
fifty or fifty-five, a gradual rise until sev- 
enty-five or eighty, and a final slight decline. 

Tuberculosis morbidity and mortality 
rates among the young age groups have 
shown marked decline in most countries 
during the past six decades. That decline, 
however, has not been maintained for older 
segments of the populations. If accidents, 
acts of war, homicide, suicide, and malig- 
nancies are excluded, tuberculosis is still one 
of the leading causes of death in the fifteen 
to forty-four age group. 

Estimates of tuberculosis deaths in vari- 
ous countries have been calculated by the 
World Health Organization (WHO). During 
1990 an estimated 2.53 million deaths from 
the disease occurred worldwide, of which 
116,000 were associated with human immu- 
nodeficiency virus (HIV) infection. Should 
the current trend continue, the WHO esti- 
mates that about 3.5 million deaths will oc- 
cur in the year 2000, approximately 500,000 
of which will be associated with HIV. Pre- 
dictions are that about half of the TB-HIV 
deaths will occur in sub-Sahara Africa. 5 Ta- 
ble 1 shows estimates of tuberculosis deaths 
in the years 1990, 1995, and 2000, including 
those that would be HIV-related. Most of the 
burden will be carried by Southeast Asia, 
Africa, and the Western Pacific regions. The 
percentage of HIV-associated deaths is ex- 



44 The Tuberculosis Story: From Koch to the Year 2000 



pected to rise from 4.6 percent in 1990 to 14.2 
percent in the year 2000. 6 

With the emergence of AIDS in the early 
1980s, the preexisting mortality peak among 
the elderly has been accompanied by a new 
peak in the twenty to forty-nine age group. 
By 1990 in the United States, 54.2 percent of 
deaths from tuberculosis in that age group 
also had AIDS on the death certificates. A 
sizeable difference has also been noted in the 
death rates between white and nonwhite 
patients. Of AIDS deaths in 1990, 1.6 percent 
of whites died with tuberculosis, compared 
to 4.7 percent of blacks and 4.7 percent of 
Hispanics. 7 



Co-infection with HIV has added another 
dimension to the tuberculosis dilemma. 
Nosocomial transmission of the Mycobac- 
terium tuberculosis (M. tuberculosis) became a 
serious problem in the last decade among 
hospitalized AIDS patients. That problem 
was further compounded by the emergence 
of multidrug-resistant (MDR) strains that 
required prolonged therapy and the possi- 
ble lengthening of the communicability pe- 
riod. 

Table 2 shows tuberculosis mortality and 
morbidity in the United States from 1955 to 
1993. The mortality rate per 100,000 dropped 
from 9.1 in 1955 to 0.6 in 1993, a decrease of 



Table 1 

Estimated Total Tuberculosis Deaths and the Total HIV-Related Tuberculosis Deaths, 1990-2000 



REGION 


1990 


1995 


2000 


Southeast Asia 


T 1,087,000 
HIV 23,000 


T 1,225,000 
HIV 88,000 


T 1,383,000 
HIV 200,000 


Western Pacific 


T 644,000 
HIV 7,000 


T 716,000 
HIV 11,000 


T 789,000 
HIV 24,000 


Atrica 


T 393,000 
HIV 77,000 


T 581.000 
HIV 150,000 


T 823,000 
HIV 239,000 


Eastern Mediterranean 


T 249,000 
HIV 4,000 


T 290,000 
HIV 6,000 


T 338,000 
HIV 15,000 


Americas2 


T 114,000 
HIV 4,000 


T 121,000 
HIV 9,000 


T 129,000 
HIV 32,000 


Eastern Europe 
and others3 


T 29,000 
HIV 200 


T 30,000 
HIV <600 


T 32,000 
HIV <900 


Western Europe 
and others'! 


T 14,000 
HIV <500 


T 14,000 
HIV 1,000 


T 15,000 
HIV 2,000 


All Regions 


T 2,530,000 
HIV 116,000 


T 2,977,000 
HIV 266,000 


T 3,509,000 
HIV 500,000 


Percentage HIV 
attributed 


4.6 


8.9 


14.2 



source: Centers for Disease Control and Prevention, "Estimates of Future Global Tuberculosis Morbidity and 
Mortality," Morbidity and Mortality Weekly Report 42 (1993): 961-64. 

1. Includes all countries of WHO except Japan, Australia, and New Zealand. 

2. Includes all countries of WHO except the United States and Canada 

3. Includes all independent states of the former Soviet Union. 

4. Western Europe and the United States, Canada, Australia, Japan, and New Zealand. 



Table 2 

Tuberculosis Morbidity and Mortality in the United 

States, 1955-1993 



YEAR 


CASES 


DEATHS 


Number 


Rate per 
100,000 


Number 


Rate per 
100,000 


1955 


77368 


46.9 


15016 


9.1 


1960 


55494 


30.8 


10866 


6.0 


1965 


49016 


25.3 


7934 


4.1 


1970 


37137 


18.3 


5217 


2.6 


1975 


33989 


15.9 


3333 


1.6 


1980 


27749 


12.3 


1978 


0.9 


1985 


22201 


9.3 


1752 


0.7 


1990 


25701 


10.3 


1810 


0.7 


1993 


25287 


9.8 


1530 


0.6 



93 percent. In the United States, as in most 
developed countries, the tuberculosis prob- 
lem has been mostly concentrated in such 
large urban centers as New York City. The 
tuberculosis mortality rate in New York City 
in 1955 was 13.9 per 100,000; in 1993 it was 
2.3 per 100,000. The latter rate is still almost 
quadruple the national tuberculosis mortal- 
ity rate. 8 

Morbidity Rates 

With the gradual decline in mortality 
from most infectious diseases in the past five 
decades, mortality statistics are no longer 
satisfactory indices of disease endemicity; 
more reliance has to be placed on morbidity 
trends, especially when comparing morbid- 
ity statistics of one country with another. In 
international comparisons, the use of tuber- 
culosis morbidity statistics is influenced by 
a multitude of factors: (1) the completeness 
of reporting, and whether it is mandatory; 
(2) the differences in the criteria that define 
a tuberculosis case (some countries report 



only bacteriologically-confirmed cases, 
while others report only respiratory tuber- 
culosis); and (3) the availability of programs 
for organized case-finding. 

WHO estimates of worldwide tuberculo- 
sis indicate that between 1990 and 1999, 88 
million tuberculosis cases are expected to 
occur, of which eight million will be associ- 
ated with HIV. During the same period, 
thirty million people are expected to die of 
tuberculosis, including 2.9 million attribut- 
able to HIV infection. The agency further 
predicts that the annual incidence of new 
cases will increase from the 7.5 million (143 
per 100,000) in 1990 to 10.2 million (163 per 
100,000) in 2000. 9 

In spite of the variability in reporting, sur- 
veillance, and case-finding, many countries 
in Africa, Asia, and South America are expe- 
riencing extremely high morbidity rates. In 
1990, morbidity rates exceeding three hun- 
dred per 100,000 have been reported from 
Zambia and Boliva and exceeding two hun- 
dred per 100,000 from the Philippines, South 
Africa, Peru, Nigeria, and India. All evi- 
dence points to a devastating tuberculosis 
toll in most African countries. 10 

In Tanzania, five thousand more cases 
were reported in 1988 over the yearly aver- 
age than during the preceding decade. In a 
rural Malawi hospital, for example, tubercu- 
losis admissions increased by 160 percent 
between 1983 and 1988. Extrapulmonary tu- 
berculosis was more frequently reported 
among younger patients. One study found 
that the prevalence of HIV infection in am- 
bulatory patients with tuberculosis in Abid- 
jan, Ivory Coast, increased from 25 percent 
in 1988 to 45 percent in 1990. u 

Table 3 shows tuberculosis notification 
rates in selected European countries in 1975, 
1980, 1985, and 1990. Generally speaking, a 
marked decline occurred in most countries 



46 The Tuberculosis Story: From Koch to the Year 2000 



TABLE 3 

Tuberculosis Notification Rates 

per 100,000 Population, 1975-1990 



COUNTRY 


1975 


1980 


1985 


1990 


Austria 


32 


29 


19 


20 


Belgium 


44 


27 


20 


16 


Finland 


74 


47 


37 


16 


France 


48 


32 


21 


16 


Germany 


51 


38 


26 


18 


Ireland 


37 


34 


23 


18 


Italyi 


7 


6 


7 


7 


Netherlands 


16 


12 


9 


9 


Portugal 


100 


70 


68 


60 


Spain2 


9 


13 


28 


19 


Sweden 


18 


11 


8 


7 


Switzerland 


33 


18 


15 


18 


United 
Kingdom 


23 


19 


12 


10 



source: P. J. Dolin et al., "Global Tuberculosis In- 
cidence and Mortality during 1990-2000," Bulletin 
of the World Health Organization 72 (1994): 213-20. 

1. Bacteriologically confirmed cases. 

2. Pulmonary tuberculosis only. 



during that fifteen-year period (except in 
Spain), and the majority of cases occurred 
among the elderly. The exception was Por- 
tugal, where more than half occurred within 
the fifteen to forty-four age range. 12 Yearly 
morbidity rates showed a modest increase 
(ranging from 5 percent in Austria and the 
United Kingdom to 27 percent in Italy) 
among industrialized countries between the 
late 80s and early 90s. 13 

In developed countries, the traditional 
risk factors associated with tuberculosis 
morbidity and mortality still play an impor- 
tant role — poverty, overcrowding, home- 
lessness, large household size, and ethnicity. 



Most cases are concentrated in large urban 
centers, where, in addition to the traditional 
environmental risk factors, there is a higher 
prevalence of HIV infections and a higher 
concentration-of immigrants from develop- 
ing countries. 

Tuberculosis morbidity rates in the 
United States dropped from 46.9 per 100,000 
in 1955 to 9.8 per 100,000 in 1993. Unfortu- 
nately, that drastic decline was not seen in 
large metropolitan areas; New York City 
had an incidence rate of 44.2 per 100,000 in 
1993 — a rate 450 percent higher than the 
national rate. 14 

The proportion of foreign-born tuberculo- 
sis cases in the United States reportedly rose 
from 21.6 percent in 1986 to 29.6 percent in 
1993. Most of the foreign-born patients were 
from Latin America and Southeast Asia. The 
tuberculosis incidence rate among foreign- 
born immigrants measured within five 
years of their immigration almost quadru- 
pled that of native residents. 15 The same 
phenomenon was observed in other indus- 
trialized countries. During 1990, 51 percent 
of all cases in Switzerland, 41 percent in the 
Netherlands, and 38 percent in Denmark 
occurred among foreign-born immigrants. 16 

Prevalence of Infection 

In spite of the gradual decline in tubercu- 
losis mortality and morbidity that occurred 
in many countries between 1950 and 1985, 
infection rates remained relatively high. The 
WHO estimated that in 1990 there were 1.7 
billion people (or one third of the world 
population) infected with the tubercle bacil- 
lus. During the early 1950s, tuberculosis 
eradication was seriously considered as an 
attainable objective. The WHO Expert Com- 
mittee set as its goal the control of the spread 
of infection to the extent that no more than 



Mahfouz H. Zaki and Mary E. Hibberd 47 



one percent of fourteen-year-old children in 
a country would react positively to a standard 
intermediate dose of tuberculin. 17 

A glance at the New York City tuberculin 
testing program among high school admis- 
sions aged thirteen to fifteen years during 
that period showed that the percentage of 
positive reactors to the Mantoux test varied 
from 10 percent in the 1959-1960 academic 
year, to 9.4 percent in 1960-1961 year, 12.5 
percent in 1961-1962, and 17.1 percent in 
1963-1964. 18 In California, positive reactor 
rates of 6 percent to 6.9 percent were re- 
ported between 1956 and 1959. 19 A long- 
term study of medical students in Chicago 
between 1939 and 1961 reported on the 
trend of tuberculous infection as indicated 
by reactions to low (two tuberculin units) 
and to high (100 tuberculin units) doses of 
tuberculin. 20 The study indicated that there 
had been a significant decrease in reactions 
to the low dose and a significant rise in 
high-dose reactions. The authors came to the 
conclusion that infection rates were still high 
despite declines in mortality and morbidity. 

Thirty years later, infection rates contin- 
ued to be high among minority groups, im- 
migrants from highly endemic countries, 
persons with HIV infection, and other spe- 
cial groups. The changing epidemiology of 
tuberculosis in the last decade changed the 
interpretation of induration on the Mantoux 
test. An induration of five or more millime- 
ters is now considered positive in those sus- 
pected of being HIV-positive, intravenous 
drug abusers, contacts of infectious cases, 
and those with radiographic abnormalities. 
An induration of ten or more millimeters is 
positive among persons born in highly en- 
demic countries, health care workers ex- 
posed to high-risk individuals, children 
younger than four years, migrant workers, 
the homeless, and in the presence of other 



medical conditions. An induration of fifteen 
or more millimeters is positive among those 
with none of the risk factors mentioned pre- 
viously. 

The University of California at Los Ange- 
les requires nonimmigrant foreign students 
to have a tuberculin test prior to registration. 
One study reported that of 589 students 
tested, 57.6 percent reacted positively to tu- 
berculin (five millimeters of induration or 
greater). 21 Prevalence of infection was also 
studied in a random sample of farmworkers 
in North Carolina in 1991. Positive reactions 
there ranged from 33 percent in Hispanics, 
to 54 percent in American blacks, to 76 per- 
cent in Haitians. 22 

A study on prevalence of tuberculosis in- 
fection and prophylaxis among a sample of 
physicians at Barnes Hospital of St. Louis 
found that of the 351 physicians tested, 
nearly a quarter (eighty-six) were skin-test 
positive by history or by a currently per- 
formed skin test. Of forty physicians eligible 
for prophylaxis, only fifteen (37.5 percent) 
completed at least six months of therapy. Of 
290 physicians previously negative, twenty- 
five (8.6 percent) tested positive. The 
authors concluded that tuberculous infec- 
tion had become common among physi- 
cians. 23 Other studies among health care 
workers showed them to be at high risk of 
infection, especially if they were HIV posi- 
tive. 

Infection rates are staggeringly high in 
developing countries. A 1992 survey from 
Lima, Peru, found that of the 368 individuals 
tested, 34 percent had indurations of ten or 
more millimeters. Stratified by age, the re- 
sults showed 12 percent positive reactors 
among children under two years of age, 18 
percent for those between two and five, 60 
percent for those between five and fifteen 
years, and 68 percent for those over twenty- 



48 The Tuberculosis Story: From Koch to the Year 2000 



five years. Vaccination with Bacillus Cal- 
mette-Guerin (BCG) was responsible for the 
weak reactions. 24 A survey of 7,721 indi- 
viduals from Saudi Arabia showed that 6 
percent of the children five to fourteen years 
of age were positive reactors to the Mantoux 
test. Children living in urban areas had a 
higher positive reactor rate (10 percent) than 
those in rural areas (2 percent). The authors 
attributed the difference to the million pil- 
grims who every year visit urban areas. :? 

A survey in sub-Sahara Africa concluded 
that a majority of adults might be infected 
with M. tuberculosis. The annual tuberculin 
conversion rate (i.e., from negative to posi- 
tive on the Mantoux test) in that region was 
estimated in the range of 1.5-2.5 percent. 
Moreover, there was a direct correlation be- 
tween the annual infection rate and the an- 
nual incidence of sputum-smear positive 
tuberculosis. 26 

The Afghanistan Experience 

During a sabbatical leave in 1971 and 
1972, one of the authors, Mahfouz Zaki, was 
on assignment by the United States State 
Department as Peace Corps Physician and 
Advisor in Public Health to the Royal Gov- 
ernment of Afghanistan (RGA). Apart from 
being responsible for the delivery of medical 
and preventive services to the volunteers 
and staff, one of his main charges was the 
promotion and initiation of public health 
programs in cooperation with the Afghan 
government. Of major public health concern 
were the extremely high birth rate and infant 
mortality rate. A family planning program 
incorporating maternal and child health was 
proposed to the RGA by Peace Corps/Af- 
ghanistan and the U.S. Agency for Interna- 
tional Development. The program was 
accepted and was funded by Peace 
Corps/ Washington. 



The other outstanding problem was tu- 
berculosis control. Despite the lack of vital 
statistics, rough estimates and special sur- 
veys demonstrated a strikingly high preva- 
lence of tuberculous infection and disease in 
rural as well as urban populations. The tu- 
berculosis problem and its extent and im- 
pact on the socioeconomic condition of the 
country had been recognized by Afghan 
public health authorities and the medical 
profession. Organized anti-tuberculosis ac- 
tivities had started only in 1954, however, 
with the establishment of the Tuberculosis 
Center in the capital, Kabul. In 1962 a plan 
of operation for tuberculosis advisory serv- 
ices was signed by the RGA and the WHO 
for the further development and expansion 
of tuberculosis control. As part of that plan 
a WHO medical officer was assigned and a 
limited direct BCG vaccination program 
was begun in the capital and in a few prov- 
inces. 

Over a two-month period Zaki visited all 
the Afghan health centers involved in tuber- 
culosis control. Organized community case- 
finding programs were practically 
nonexistent. Patients were usually discov- 
ered only after they had sought medical at- 
tention for prolonged respiratory 
symptoms. Diagnosis was made through 
smear examination and, on occasion, chest 
x-ray. Culture was infrequently resorted to 
in questionable cases and was performed 
only by the Institute of Public Health in 
Kabul, which acted also as a reference labo- 
ratory. The use of mass chest radiography, a 
productive case-finding tool in areas of high 
prevalence, was not well utilized because of 
the scarcity of x-ray machines and lack of 
film. 

Tuberculin testing was not used for case- 
finding because in areas of such high preva- 
lence the majority of the adult population 



Mahfouz H. Zaki and Man- E. Hibberd 49 



would have reacted positively to tuberculin 
and thus nullify its use for case-finding. 
Even at the family level in private practice, 
however, tuberculin testing was not usually 
performed. After diagnosis, patients were 
treated in municipal hospitals or by private 
practitioners on an ambulatory basis with 
isoniazid and thiacetazone. Therapy was 
usually for a short period, two to three 
months on the average; in only a few in- 
stances did the author find therapy contin- 
ued for more than one year. Hospitalization 
was limited to patients with advanced dis- 
ease or those with complications. Patients 
were usually encouraged, directly or indi- 
rectly, to continue with their therapy 
through private practitioners. Many pa- 
tients did not have access to or could not 
afford private medical care, and their ther- 
apy was thus interrupted. Moreover, sup- 
plies and drugs were scarce, even in the 
municipal hospitals and health centers. Dur- 
ing 1971 there were only 1,248 patients on 
the tuberculosis register in Kabul and the 
eleven provinces where control efforts were 
in operation. Considering the magnitude of 
the tuberculosis problem in Afghanistan, 
one could safely conclude that case-finding 
and chemotherapy were not employed to 
any meaningful extent. 

Direct BCG vaccination (i.e., without prior 
tuberculin testing) was used for those under 
twenty years of age. The vaccine was mostly 
supplied by the United Nations Children's 
Fund. In many of the centers visited by the 
author, however, the vaccine was not avail- 
able; and in most situations, coverage was 
incomplete. Chemoprophylaxis with 
isoniazid was rarely employed for the pro- 
tection of household contacts or high-risk 
individuals. 

In an attempt to obtain reliable estimates 
of the prevalence of tuberculosis and histo- 



plasma infections and in response to a re- 
quest from the RGA, Peace Corps/Afghani- 
stan undertook an extensive prevalence 
survey in cooperation with the Centers for 
Disease Control and Prevention (CDC). The 
survey included all 1,030 incoming fresh- 
men at Kabul University in the fall of 1971. 
Most of the students (93 percent) were males 
and most (96 percent) were between fifteen 
and twenty-four years of age. Each student 
was injected with four antigens supplied by 
the Tuberculosis Branch of the CDC. One 
antigen was from human strains of M. tuber- 
culosis (five tuberculin units), one from an 
atypical strain (Battey bacilli), one from His- 
toplasma capsidatum, and one from Candida 
albicans. A double-blind approach was used. 
The antigens were color coded and were 
injected in doses of .10 ml by 26-gauge plati- 
num needles in four sites in the two upper 
arms. Tests were read after seventy-two 
hours. 

Conducting the prevalence survey was a 
fascinating experience. Following procure- 
ment of the antigens and other medical sup- 
plies from the CDC, the author was faced 
with a serious problem — the recruitment of 
staff to administer four intradermal antigens 
per person to more than 3,500 individuals 
(in addition to the university students, the 
survey included outpatients and elementary 
schoolchildren). The author and his wife (a 
registered nurse who volunteered to partici- 
pate) were the only medical or nursing 
Peace Corps staff available. Fortunately, he 
was able to recruit the vacationing niece of 
an American Consortium surgeon at Uni- 
versity Hospital, who also happened to be a 
registered nurse. One physician and two 
nurses could scarcely administer more than 
fourteen thousand intradermal injections, 
however, and so assistance was sought from 
nonmedical Peace Corps volunteers. Twelve 



50 The Tuberculosis Story: From Koch to the Year 2000 



Table 4 

Tuberculin Sensitivity Survey at Kabul University, Afghanistan, 1971 



Age 
Group 
(years) 


SIZE OF REACTION IN MILLIMETERS TO PPD-S 


Total 
Tested 

& Read 


0-4 


5-9 


10+ millimeters 


Number 


Percent 


Number 


Percent 


Num- 
ber 


Percent 


15-19 

20-24 

25-29 

30+ 


166 
227 

6 

3 


40.9 
39.1 
19.4 
25.0 


62 
96 

8 

1 


15.3 
16.5 
26.8 
8.3 


178 
258 

17 

8 


43.8 
44.4 
64.8 
66.7 


406 

581 

31 

12 


Total 


402 


39 


167 


16.2 


461 


44.8 


1030 


Male 
Female 


363 
39 


38.4 
46.4 


148 

19 


15.6 
22.6 


435 
26 


46.0 
31.0 


946 
84 



volunteers (architects and agriculture, mu- 
sic, and English majors) joined the survey 
team. Their crash course included an intro- 
duction to the antigens used, the reactions 
expected, and the intradermal procedures. It 
should be emphasized that the performance 
of the nonmedical volunteers in the admini- 
stration of the Mantoux tests was excellent, 
as good as any well-trained medical or nurs- 
ing staff. 

The language barrier made it difficult to 
get accurate information relating to pre- 
vious BCG vaccination. The question, there- 
fore, was whether the student had had any 
previous immunization. (Preventive meas- 
ures, including childhood immunizations, 
were hardly performed in Afghanistan.) 
BCG vaccination had been introduced 
around the Kabul area and in a few prov- 
inces, but the coverage was scattered. It was 
thus safely presumed that more than 90 per- 
cent of the students had not been vaccinated 
with BCG. The percentage of positive reac- 
tors among those with previous history of 
any immunization did not differ signifi- 
cantly from the same among those with no 
previous history of immunization. 



About 34 percent of the students had re- 
actions of four to nine millimeters to puri- 
fied protein derivate B. Because of the lack 
of information on the prevalence of infection 
with atypical strains, a conservative position 
was adopted and a reaction of ten millime- 
ters to purified protein derivate S was con- 
sidered indicative of a past tuberculosis 
infection. As is evident from Table 4, of the 
1,030 students tested, 39 percent had reac- 
tions of zero to four millimeters, 16.2 percent 
five to nine millimeters, and 44.8 percent 10 
or more millimeters to five tuberculin units 
of M. tuberculosis. 

The experience gleaned from the preva- 
lence survey shows what can be accom- 
plished bv nonmedical staff in the areas of 
public health and preventive medicine. In- 
deed, it was to the credit of Peace Corps that 
both the Family Planning and Tuberculosis 
Control programs withstood all the political 
upheaval and fiscal crises and operated suc- 
cessfully until the U.S. government pulled 
out of Afghanistan in the late seventies. Had 
a similar prevalence survey been conducted 
in the United States, it would probably have 
cost more than $100,000, and would have 



Mahfouz H. Zaki and Mary E. Hibberd 51 



taken a couple of years to procure all the 
necessary administrative and legal approvals 
in order to avoid future litigation and mal- 
practice suits. 

Infection with MDR Strains 

During the past four decades there has 
been growing concern over the prevalence 
of infections with drug-resistant strains of 
M. tuberculosis among previously untreated 
subjects, a phenomenon frequently referred 
to as "primary drug resistance." Although 
the exact nature of drug resistance and the 
intricate mechanism that leads to its devel- 
opment have not been fully elucidated, cli- 
nicians and public health physicians are 
acutely aware of the trend of infection with 
drug-resistant strains, the effect of drug-re- 
sistant strains on clinical progress of pa- 
tients, and the transmission of infection 
among their contacts. 

In this country and abroad, conflicting 
reports have been published on the preva- 
lence and trend of infection with strains re- 
sistant to the first- and second-line drugs. In 
this paper, attention is given to selected 
studies only. One of the most important con- 
tinuing surveys of drug resistance by the 
United States Public Health Service 
(USPHS) was done in cooperation with 
twenty-two state and city hospitals through- 
out the nation between 1961 and 1962. The 
survey demonstrated that out of 2,400 
strains isolated, 1.6 percent were resistant to 
isoniazid (INH), 2.8 percent were resistant to 
streptomycin (SM), and 0.8 percent were re- 
sistant to para-aminosalicylic acid (PAS). 27 

In a five-year study of drug resistance of 
1,777 isolates in New York City, researchers 
using the USPHS cooperative study criteria 
found that the rate of infection with strains 
resistant to INH increased from 11.5 percent 
of all infections in 1960 to 23.2 percent in 



1964. The increase was attributable to strains 
resistant to INH alone — 6.5 percent in 1960 
and 17.3 percent in 1964. 28 

A recent study compared drug-resistance 
patterns in the United States by geographic 
distribution, demographic characteristics, 
and risk factors. The patient population 
studied consisted of all patients with posi- 
tive cultures reported in the first quarter of 
1991. Resistance to one or more drugs was 
found in 14.2 percent of cases; resistance to 
INH and/or rifampin was found in 9.5 per- 
cent of cases whose isolates were tested 
against one or both drugs. Those cases were 
reported from thirty-three states. Resistance 
to both INH and rifampin was 3.5 percent of 
cases reported from thirteen states. The 
authors also found that MDR-TB in New 
York City was 52.4 times that of the rest of 
the nation. The relative risk among whites in 
New York City was 39.0 that of non-His- 
panic whites in the rest of the nation, 299.3 
of Hispanics, 420.9 of Asian/Pacific Island- 
ers, and 701.0 of non-Hispanic blacks. 29 

Another study described the incidence of 
MDR-TB among residents of the tuberculo- 
sis unit of the New York municipal shelter 
system. Among fifty-eight isolates of M. tu- 
berculosis, eight were resistant to one drug 
(14 percent) and an additional nine were 
resistant to at least two drugs (16 percent). A 
history of previous treatment among home- 
less men was associated with increased risk 
of having MDR. 30 

In a study of 1,181 bacteriologically-posi- 
tive cases reported between 1983 and 1992 
in Israel, researchers found that 12.6 percent 
of isolates were resistant to one drug (7.3 
percent) or more than one drug (5.3 per- 
cent). 31 The highest incidence of drug-resis- 
tant bacilli was among immigrants from the 
Soviet Union (37.3 percent) and Ethiopia 
(16.2 percent). In a 1995 study of 2,509 Aus- 



52 The Tuberculosis Story: From Koch to the Year 2000 




American nurses 
Nina Teller (at 
lefU and Kathn/n 
Zaki administer 
skin tests in Kabul, 
Afghanistan, in 
1971. 



tralian residents with bacteriologically-con- 
firmed tuberculosis, resistance to at least one 
of the common antituberculosis drugs was 
detected in 14.4 percent of isolates; resis- 
tance usually involved INH (8.4 percent) 
and SM (7.6 percent). Fewer than one per- 
cent were resistant to both INH and ri- 
fampin. 32 

A report published in 1993 from England 
and Wales showed that between 1982 and 
1991, over sixteen thousand isolates had re- 
sistant strains. 33 The proportion of initial iso- 
lates resistant to one or more drugs ranged 
from 8-10.9 percent between 1982 and 1990. 
In 1991, however, that increased to 14.2 per- 
cent. MDR, however, remained low. 

The advent of effective antibiotics and 
chemotherapeutics in the 1950s and 1960s 
had two unfortunate consequences: infec- 
tion control practices in hospitals were re- 
laxed, and nosocomial infections increased. 



By the late 1980s, the upsurge of tuberculosis 
and MDR strains were subjecting health care 
workers — especially those involved in 
cough-producing procedures — to a higher 
risk of infection. One study not only docu- 
mented outbreaks of MDR strains in twelve 
hospitals but also found conversion rates 
ranging from 18-35 percent among exposed 
health care workers. 34 

To combat the high concentrations of 
MDR strains, tuberculosis, and HIV infec- 
tions in large urban areas, the CDC devel- 
oped a National Action Plan. The plan calls 
for: (1) greater surveillance and epidemiologic 
studies of MDR-TB; (2) initiatives to improve 
the rapidity, sensitivity, and reliability of 
diagnostic methods for MDR-TB; (3) pro- 
grams to ensure the regularity and effective- 
ness of therapeutic regimens; (4) preventing 
those infected with susceptible strains from 
developing drug resistance; (5) screening 



Mahfouz H. Zaki and Man' E. Hibberd 53 



programs for identifying those at risk of de- 
veloping MDR-TB and preventing them 
from developing active disease; (6) expan- 
sion of infection control programs to reduce 
nosocomial infections; (7) training and edu- 
cation of health care workers regarding 
MDR-TB epidemiology and prevention; (8) 
outbreak control; and (9) program evalu- 
ation. 35 

The multitude of factors that play a role in 
drug resistance, whether primary or ac- 
quired, make comparative studies an ex- 
tremely difficult task. That is especially true 
today because of the lack of agreement on 
the criteria for significant drug resistance as 
well as on the most efficient or appropriate 
techniques for testing drug sensitivity. 
Whatever the absolute figures are, the most 
important fact is that there is a definite in- 
crease in infections with strains resistant to 
first-line drugs. 

More extensive epidemiologic, labora- 
tory, and clinical studies are surely needed. 
Such studies should include transmission of 
drug-resistant strains, testing techniques, 
criteria of resistance, and the relationship of 
in vitro resistance to in vivo response. It may 
also be important for the major chest disease 
services to initiate and encourage "resis- 
tance surveillance units" using uniform 
techniques and criteria to help demonstrate 
the prevalence of resistant strains. 

Regularity of Drug Administration 

The development of potent chemothera- 
peutics for the treatment of tuberculosis, 
plus the skyrocketing cost of hospitalization 
during the 1950s and 1960s, caused a shift in 
the locale of therapy from the hospital or 
sanatorium to the patient's home. That trend 
was given further impetus by the well-pub- 
licized success of ambulatory programs con- 
ducted by Wallace Fox in Madras, India, in 



the late 1950s, which were supported by the 
British Medical Research Council. 36 

With the adoption of domiciliary treat- 
ment, the question of regularity of drug ad- 
ministration was often raised. The regimen 
of choice for such treatment was one or two 
years of therapy with SM, INH, and PAS. 
Studies conducted in this country and 
abroad showed that hospitalized patients 
took their medication more regularly than 
those under domiciliary treatment. 

In a study of the regularity of drug ad- 
ministration by Zaki and others, tuberculo- 
sis patients hospitalized at Kings County 
Hospital Center, Brooklyn, were matched 
with an equal number of comparable pa- 
tients treated on an ambulatory basis by the 
health department chest disease clinics. All 
patients were being treated with INH and 
PAS. Surprise visits were made to obtain 
urine samples from both groups in order to 
determine whether they differed signifi- 
cantly in the regularity of INH and PAS 
administration. Researchers found that 96 
percent of the hospitalized patients were 
taking both drugs on the day of examina- 
tion, whereas only 56 percent of the ambula- 
tory patients were taking INH and 52 
percent of them were taking PAS. 37 A similar 
study reported that 90 percent of hospital- 
ized patients took PAS regularly, compared 
with only 35.5 percent of ambulatory pa- 
tients. Neves Almeida reported from Portu- 
gal that 70 percent of 1,306 inpatients and 47 
percent of 469 outpatients had urine-posi- 
tive results for PAS. 38 

All of those studies pointed to the inade- 
quacies of ambulatory treatment of tubercu- 
losis patients, which resulted in the 
development of MDR and a high relapse 
rate. The authors also advocated either an 
initial hospitalization period to train or con- 
dition the patient to follow the necessary 



54 The Tuberculosis Story: From Koch to the Year 2000 



regimen or upgrade and closely supervise 
drug administration in the ambulatory set- 
ting. The practice of directly observed ther- 
apy (DOT) was introduced in the 1980s and 
recommended as an integral part of a tuber- 
culosis control program. The comparison of 
incidence of drug resistance and relapse 
among tuberculosis patients in Tarrant 
County, Texas, prior to and after the institu- 
tion of DOT was encouraging. Between 
January 1980 and October 1986, 407 patients 
with positive cultures received traditional 
treatment; between 1986 and 1992, 581 pa- 
tients received medication under DOT. The 
authors noted that despite the higher rate of 
intravenous drug use and homelessness 
during the thirteen-year study period, the 
frequency of primary drug resistance de- 
creased from 13 percent to 6.7 percent after 
the institution of DOT, and the frequency of 
acquired drug resistance declined from 14 
percent to 2.1 percent. The number of re- 
lapses with MDR organisms decreased from 
twenty-five to five. The authors concluded 
that DOT significantly reduced both the re- 
lapse rate and the frequency of primary and 
acquired drug resistance. 39 

Currently recommended therapy for 
patients infected with susceptible strains 
consists of INH, rifampin, and pyrazi- 
namide for two months, followed by INH 
and rifampin for four months. Ethambutol 
or SM should be included in the initial treat- 
ment pending sensitivity studies. Such four- 
drug therapy over a six-month period is 
effective even if the infecting strain is resis- 
tant to INH. Treatment of MDR infections, 
however, must be individualized. If the 
strain is resistant to first-line drugs, second- 
line drugs may have to be used and treat- 
ment may be extended to twenty-four 
months. Caution should be taken to monitor 
side reactions since most second-line drugs 



are not as well tolerated as first-line drugs. 
Today more than ever, the emergence of 
MDR strains and the standard short-term 
therapies mandate the deployment of DOT. 

Co-Infection with HIV 

The incidence of tuberculosis is substan- 
tially increased in HIV-infected individuals. 
As a matter of fact, the TB/HIV co-infection 
is the fastest-growing epidemic. It has been 
estimated that tuberculosis occurs five hun- 
dred times more frequently in HIV-infected 
individuals than in the general population. 40 
The WHO estimated that approximately 
four million people had been infected with 
both the M. tuberculosis and HIV since the 
beginning of the pandemic. Of those, 95 per- 
cent were in developing countries. 41 The im- 
pact on Africa and Asia has been 
devastating. Since the 1980s, the annual 
number of TB cases with HIV co-infection 
has nearly tripled in Zambia and more than 
doubled in Malawi. 42 In 1990 co-infection 
represented 4.2 percent of all tuberculosis 
cases, and predictions are that it would ac- 
count for 8.4 percent in 1995 and 13.4 by the 
year 2000 . 4? 

Surveillance data reported to the CDC 
during 1981-1994 indicated that among 
441,528 persons reported to have AIDS, 
20,136 (4.6 percent) had extrapulmonary tu- 
berculosis and 6,432 (1.4 percent) had pul- 
monary tuberculosis. 44 A United States 
study of AIDS/TB dual infections from 1981 
through 1991 concluded that "the risk of TB 
or AIDS among persons diagnosed with one 
disease is much higher than the general 
population." The authors further estimated 
that the immunosuppression caused by the 
HIV infection might have accounted for at 
least 30 percent of new TB cases between 
1985 and 1990. 45 A study of INH prophylaxis 
on the incidence of active tuberculosis and 



Mahfouz H. Zaki and Marv E. Hibberd 55 



the progression of HIV infection in Port-au- 
Prince, Haiti, reported that the drug effectively 
decreased the incidence of tuberculosis and 
delayed the onset of HIV-related disease in 
symptom-free HIV-seropositive individu- 
als. 46 INH was also shown to be an effective 
prophylactic for HIV-infected tuberculin re- 
actors and for many HIV-infected anergic 
patients. 47 

Although primary tuberculosis has oc- 
curred occasionally in HIV-infected indi- 
viduals, the majority of clinical tuberculosis 
in that population is due to a reactivation of 
a latent infection. That underscores the need 
for tuberculin testing of drug injectors with 
known or suspected HIV infection and the 
administration of INH prophylaxis for both 
the anergic and tuberculin-positive reactors. 
TB/HIV infections changed the tuberculosis 
mortality pattern dramatically. Prior to the 
AIDS era, the tuberculosis mortality peak 
was among the elderly. Now, another peak 
has emerged among patients twenty to 
forty-nine years of age, resulting in a bimo- 
dal mortality curve. The co-infection di- 
lemma has been further compounded by the 
frequent infection with MDR strains and the 
occurrence of epidemics. 

Prospects for Eradication 

Experience with tuberculosis has demon- 
strated that effective control cannot be 
achieved simply by the development of 
chemotherapeutic drugs or attempts at early 
case-finding. An illustration is the story of 
sexually-transmitted diseases. Following 
the introduction of penicillin with its dra- 
matic effect on gonorrhea and syphilis over 
fifty years ago, elimination of at least those 
two diseases was considered to be a one- 
decade operation. Instead, more than 
500,000 cases are yearly reported to the 
CDC, a figure that is probably only half or 



even a third of the total number of cases. The 
upsurge of primary and secondary syphilis 
between 1988 and 1992 in large metropolitan 
areas in this country demonstrates the diffi- 
culties encountered in the elimination proc- 
ess. 

Believers in the "No Tuberculosis by 1960" 
slogan were confident that the marked de- 
cline in tuberculosis mortality and the rela- 
tive decline in morbidity would result in 
eradication, and their predictions were sub- 
stantiated by various mathematical models. 
Many of those models were based on very 
rough estimates of infection and relapse 
rates, however, and on the results of early 
chemoprophylactic trials. Incidence rates 
were projected as a function of large-scale 
application of various control measures, in- 
cluding effective chemoprophylaxis of all 
infected individuals or even mass BCG vac- 
cination of children. Considering the many 
determinants that are incorporated in tuber- 
culosis epidemiology and the difficulty that 
may be encountered in enforcing control 
measures of that nature on a mass basis, one 
would be inclined to question the validity of 
such models. Today the tuberculosis situ- 
ation in Africa, Asia, Central America, South 
America, and some urban centers in devel- 
oped countries is far from encouraging; in- 
fection rates in the child population may 
reach as high as 30 or 40 percent. Talk of 
eradication in those countries seems quite 
premature. 

Funding for tuberculosis programs dur- 
ing the 1960s and 1970s was handicapped by 
misleading inferences concerning the reso- 
lution of the tuberculosis problem. Whether 
in this country or worldwide, funding dwin- 
dled to an embarrassing level. Of the $811 
million in foreign aid to the WHO in 1990, 
only $16 million was allocated for tubercu- 
losis, the least amount spent on an infectious 



56 The Tuberculosis Story: From Koch to the Year 2000 



disease. 48 The decline of appropriations for 
tuberculosis control by the United States 
government and the State of New York over 
the past fifteen years are shown in Table 5. 49 
It is difficult to believe that the richest and 
most technologically advanced country in 
the world would appropriate $3.6 million 
for tuberculosis control in 1980 for a popu- 
lation of more than 230 million. 

Relaxation of control measures and reduc- 
tion of funding for a declining disease are 
among the most common errors in preven- 
tive medicine and public health policy deci- 
sion-making. It is at that stage of decline 
when all available tools should not only be 
deployed but augmented. A swift massive 
assault could thus be directed toward the 
remaining pockets of infection, leading to 
the eventual elimination of the disease. The 
cost of the resurgence of tuberculosis has 
been astronomical. For illustration, between 
1979 and 1994 approximately twenty thou- 
sand new tuberculosis cases occurred in 
New York City. Those cases would not have 
occurred had the previous declining trend 
continued. The total cost of care for those 
patients exceeded $400 million. 50 In addi- 
tion, the cost of hospitalizing about one third 
of those patients (in addition to expendi- 
tures for hospital renovations and prophy- 
lactic therapy) pushed the final cost in excess 
of one billion dollars. 

Serious funding should be allocated for 
the following objectives: 

• Search for new chemotherapeutics for 
the treatment of MDR-TB (existing 
treatment regimens require the admini- 
stration of four to six agents that are not 
always well tolerated). 

• Establish DOT as the standard of care, 
especially for MDR strains. 



Table 5 

Federal and New York State Tuberculosis Control Appropriations 



YEAR 


UNITED STATES 


STATE OF NEW YORK 


Incidence 


Funding 


Incidence 


Funding 


1980 
1985 
1990 
1991 
1992 
1993 
1994 
1995 


27,769 
22,201 
25,701 
26,283 
26,673 
25,287 
24,361 


$ 3,600,000 

9,250,000 

22,533,000 

25,274,000 

46,486,000 

104,298,000 

142,232,000 

145,045,000 


2,294 
2,481 
4,176 
4,421 
4,574 
3,952 
3,636 


$4,377,600 

514,304 

1,738,450 

2,855,000 

8,739,053 

29,573,466 

31 ,497,467 

32,690,822 



• Initiate screening programs, especially 
for high-risk individuals and those 
older than fifty years of age. 

• Conduct proper case management to 
ensure that patients follow their thera- 
peutic regimens. 

• Initiate tuberculosis infection control 
measures for health care facilities. 

• Begin selective BCG vaccination programs. 

Winning the fight against disease is analo- 
gous to winning a war, and no one could 
explain that concept more eloquently than 
General Douglas MacArthur in his address 
to the joint session of Congress on April 19, 
1951: 

[OJnce war is forced upon us, there is no 
other alternative than to apply every available 
means to bring it to a swift end. War's very 
object is victor}' — not prolonged indecision. In 
war, indeed there can be no substitute for vic- 
tory. 

For history teaches us with unmistakable 
emphasis that appeasement but begets new 
and bloodier war. It points to no single in- 
stance where the end has justified that 
means — where appeasement has led to more 
than sham peace. Like blackmail, it lays the 
basis for new and successively greater demands, 



Mahfouz H. Zaki and Marv E. Hibberd 57 



until as in blackmail, violence becomes the 
only other alternative. 51 

Unfortunately, tuberculosis had lost its 
constituency and intrigue by the 1970s. 
Elected officials and budget officers used the 
declining morbidity and mortality to reduce 
appropriations for tuberculosis control. 
Those reductions resulted in the weakening 
of already-mediocre programs in case-find- 
ing, supervision of drug administration, 
prophylaxis, and follow-up. MDR strains 
emerged, combining with HIV to cause an 
upsurge of tuberculosis as a major public 
health problem. 

The current tuberculosis crisis is totally 
different from the earlier tuberculosis sce- 
nario. Previously, most mycobacterial 
strains were susceptible to first-line drugs, 
there was no concomitant HIV infections, 
and specialized hospitals or sanatoria of- 
fered supervised therapy. Today, many tu- 
berculosis patients are infected with MDR 
strains, have concomitant HIV infection, 
and are treated at home; some are poverty 
stricken or homeless and have no access to 
appropriate medical care. 

Many factors, both epidemiological and 
social, will impede the elimination process: 
the pathological nature of tuberculosis; its 
chronicity; the ability of the tubercle bacillus 
to remain alive in the human body for years; 
the changing patterns of morbidity and mor- 
tality among age groups; increased life ex- 
pectancy; the high prevalence of active 
disease and infection rate in developing 
countries and in select groups in developed 
countries; the alarming increase in MDR 
strains; the concomitant infection with HIV; 
the relatively high reactivation rate; and the 
changing epidemiology of tuberculosis, in- 



cluding the recent occurrence of epidem- 



ics. 52 

The past two decades have witnessed a 
dramatic emphasis on environmental con- 
taminants and their impact on human 
health. The wide publicity given incidents 
such as the Love Canal in New York State 
and the possible deleterious effects of expo- 
sure to Agent Orange have heightened pub- 
lic awareness and, in a sense, engendered a 
state of environmental paranoia. Our society 
seems to be willing to accept tangible and 
measurable risks resulting from such infec- 
tions as M. tuberculosis, cigarette-smoking, 
and excessive alcohol intake. The same soci- 
ety, however, is unable to tolerate potential, 
intangible, and unmeasurable risks from 
food additives, pesticides, air pollutants, 
and water contaminants. The fascination 
with environmental contaminants by politi- 
cians and the public at large has resulted in 
the misappropriation of billions of dollars 
for the environment at the expense of such 
basic intrinsic needs as tuberculosis control. 

The failure of this country to contain the 
tuberculosis problem is unfortunate, short- 
sighted, and disgraceful. The United States 
should set an example for the whole 
world — not only by embarking on an all-out 
offensive against the tuberculosis problem 
in this country but also by providing sub- 
stantial funding to the WHO for combating 
the disease worldwide. It cannot be overem- 
phasized that a sizeable proportion of tuber- 
culosis patients in developed countries are 
immigrants from highly endemic areas. In 
other words, our assistance to the interna- 
tional effort will eventually benefit the 
United States. 



58 The Tuberculosis Story: From Koch to the Year 2000 



Notes 



1 . L.I. Dublin, "No More Tuberculosis by 1960," 
Survey Graphics 46 (1941): 33-36. 

2. J. A. Perkins, "Global Tuberculosis Eradica- 
tion," American Review of Respiratory Disease 80 
(1959): 138-39. 

3. The Arden House Conference on Tuberculo- 
sis, Harriman, N.Y., United States Public Health 
Service, Department of Health, Education and Wel- 
fare, 1959. 

4. F. L. Soper, "Problems to Be Solved if the 
Eradication of Tuberculosis Is to Be Realized," 
American Journal of Public Health 52 (1962): 724-45. 

5. Centers for Disease Control and Prevention, 
"Estimates of Future Global Tuberculosis Morbidity 
and Mortality," Morbidity and Mortality Weekly Report 
42 (1993): 961-64. 

6. Ibid. 

7. M. M. Braun, T. R. Cote, and C. S. Rabkin, 
"Trends in Death with Tuberculosis during the 
AIDS Era," JAMA 269 (1993): 2865-68. 

8. Centers for Disease Control and Prevention, 
USPHS, personal communication to the authors, 
1995; Bureau of Tuberculosis Control, Department 
of Health, City of New York, personal communica- 
tion to the authors, 1995. 

9. P. J. Dolin, M. C. Raviglione, and A. Kochi, 
"Global Tuberculosis Incidence and Mortality dur- 
ing 1990-2000," Bulletin of the World Health Organiza- 
tion 72 (1994): 213-20. 

10. World Health Organization, Report on the TB 
Epidemic: TB, A Global Emergency (Geneva:WHO, 
1994). 

11. K. M. DeCock et al., "Tuberculosis and HIV 
Infection in Sub-Saharan Africa," JAMA 268 (1992): 
1581-87. 

12. Dolin et al., "Global Tuberculosis Incidence." 

13. World Health Organization, Report on the TB 
Epidemic. 

14. Bureau of Tuberculosis Control, Department 
of Health, City of New York, personal communica- 
tion to the authors, 1995. 

15. M. T. McKenna, E. McGray, and I. Bronato, 
"The Epidemiology of Tuberculosis among Foreign- 
born Persons in the United States, 1986-1993," Nezv 
England Journal of Medicine 33 (1995): 229-33. 

16. Dolin et al., "Global Tuberculosis Incidence." 

17. A. Kochi, "Government Intervention Pro- 
grams in HIV/Tuberculous Infection," Bulletin of the 
International Union against Tuberculosis and Lung Dis- 
ease 66 (1991): 33-36. 

18. R. S. Merchant, Tuberculosis in Neu> York City 
(New York: Tuberculosis and Health Association, 
1964). 

19. F. ]. Currv, "Tuberculin Skin Testing in San 
Francisco Schools," American journal of Public Health 
52 (1962): 616-26. 



20. S. R. Rosenthal, M. J. Colbert, and I. Nikurs, 
"Tuberculin Reaction Trend and BCG Vaccination," 
Archives of Environmental Health 11 (1965): 794-803. 

21. S. "Quillan, C. K. Malotte, and D. Shlian, 
"Evaluation of a Tuberculosis Screening and Pro- 
phylaxis Program for International Students," Jour- 
nal of American College Health 38 (1990): 165-70. 

22. S. D. Ciesielski et al., "The Epidemiology of 
Tuberculosis among North Carolina Migrant Farm 
Workers," JAMA 265 (1991): 1715-19. 

23. V. J. Fraser et al., "Screening of Physicians for 
Tuberculosis," Infection Control and Hospital 
Epidemiology 15 (1994): 95-100. 

24. W. S. Getchell et al., "Basic Epidemiology of 
Tuberculosis in Peru: A Prevalence Study of Tuber- 
culin Sensitivity in Pueblo Joven," American Journal 
of Tropical Medicine and Hygiene 47 (1992): 721-29. 

25. F. A. Kassimi et al., "Nationwide Community 
Survey of Tuberculosis Epidemiology in Saudi Ara- 
bia," Tubercle and Lung Disease 74 (1993): 254-60. 

26. DeCock et al., "Tuberculosis and HIV 
Infection." 

27. U.S. Public Health Service, "Cooperative In- 
vestigation: Prevalence of Drug Resistance in Pre- 
viously Untreated Patients," American Review of 
Respiratory Disease 89 (1964): 327-36. 

28. M. H. Zakietal., "The Trend of Infection with 
Drug-resistant Strains of Mycobacterium Tubercu- 
losis among Untreated Patients," American Journal of 
Public Health 59 (1969): 2056-66. 

29. A. B. Bloch et al., "Nationwide Survey of 
Drug-resistant Tuberculosis in the United States," 
JAMA 271 (1994): 665-71. 

30. J. Concato and W. N. Rom, "Endemic Tuber- 
culosis among Homeless Men in New York City," 
Archives of Internal Medicine 154 (1994): 2069-73. ' 

31. A. Lavy and A. Mates, "A 10-vear Survey and 
Mycobacterium Tuberculosis in Israel and Their 
Drug Resistance," Israel Journal of Medical Science 30 
(1994): 805-10. 

32. D. J. Dawson et al., "Tuberculosis in Australia, 
1980-1992: Bacteriologically Confirmed Cases and 
Drug Resistance," Medical Journal of Australia 162 
(1995): 287-90. 

33. A. R. Warburton et al., "Drug Resistance in 
Initial Isolates of Mycobacterium Tuberculosis in 
England and Wales, 1982-1991," Communicable Dis- 
ease Rejiort 3 (1993): 175-79. 

34. D. Menzies et al., "Tuberculosis among 
Health Care Workers," Nrw England journal of Medi- 
cine 332 (1995): 92-98. 

35. Centers for Disease Control and Prevention, 
USPHS, "National Action Plan to Combat Mul- 
tidrug-resistant Tuberculosis," Morbidity and Mortal- 
ity Weekly Report 41 (1992): 5-48. 

36. W. Fox, "The Chemotherapy and Epidemiol- 
ogy of Tuberculosis," Lancet 2 (1962): 413-17. 

37. M. H. Zaki, S. Edelstein, R. A. Josephson, and 
S. R. Weisberg, "Regularity of Drug Administration 
among Hospitalized and Ambulatory Tuberculous 



Mahfouz H. Zaki and Mary E. Hibberd 59 



Patients," American Review of Respiratory Disease 97 
(1968): 136-39. 

38. Ibid. 

39. S. E. Weis et al., "The Effect of Directly Ob- 
served Therapy on the Rates of Drug Resistance and 
Relapse in Tuberculosis," Neiv England Journal of 
Medicine 330 (1994): 1179-84. 

40. P. F. Barnes et al., "Tuberculosis in Patients 
with Human Immunodeficiency Virus Infection," 
New England Journal of Medicine 324 (1991): 1644-50. 

41. J. P. Naraiii, M. C. Raviglione, and A. Kochi, 
"HIV Associated Tuberculosis in Developing Coun- 
tries: Epidemiology and Strategies for Prevention," 
Tubercle and Lung Disease 73 (1992): 311-21. 

42. World Health Organization, Report on tlie TB 
Epidemic. 

43. P. J. Dolin, M. C. Raviglione, and A. Kochi, 
" Estimates of Future Global Tuberculosis Morbidity 
and Mortality," JAMA 271 (1994): 739-11. 

44. Centers for Disease Control and Prevention 
Reports. 

45. D. R. Burwen et al., "National Trends in the 
Occurrence of Tuberculosis and Acquired Immu- 
nodeficiency Syndrome," Archives of Internal Medi- 
cine 155 (1995): 1281-86. 

46. J. W. Pape et al., "Effect of Isoniazid Prophy- 
laxis on Incidence of Active Tuberculosis and Pro- 
gression of HIV Infection," Lancet 342 (1993): 268-72. 

47. D. N. Rose, C. B. Schechter, and H. S. Sacks, 
"Preventive Medicine for HIV-infected Patients: An 
Analysis of Isoniazid Prophylaxis for Tuberculosis 
Reactors and for Anergic Patients," Journal of General 
Internal Medicine 7 (1992): 589-94. 

48. World Health Organization, Report on tlie TB 
Epidemic. 

49. Division of Tuberculosis Elimination, Centers 
for Disease Control and Prevention, personal com- 
munication to authors, 1995. 

50. T. R. Frieden et al., "Tuberculosis in New York 
City: Turning the Tide," Neiv England Journal of Medi- 
cine 333 (1995): 229-33. 

51. D. Clayton James, Tlie Years of MacArthur: Tri- 
umph and Disaster 1 945-1965 (Boston: Houghton Mif- 
flin Company, 1985). 

52. M. H. Zaki, "On the Epidemiology of Tuber- 
culosis in Some Selected Countries: Highlights and 
Prospects for Control and Eradication, Part 11," 
American Journal of Public Health 61 (1971): 843-54. 



Mahfouz H. Zaki is the Director of Public Health of 
Suffolk County, New York, and Clinical Professor of 
Preventive Medicine at the Health Science Center of 
the State University of New York at Brooklyn. His 
previous experience includes service as a Peace Corps 
physician and Advisor in Public Health to the Royal 
Government of Afghanistan. He was also a Lieutenant 
Colonel in the U.S. Army Medical Corps Reserve. 



Mary Elizabeth Hibberd is the Commissioner of the 
Suffolk County Department of Health Services and a 
member of the New York State Public Health Council. 
She is also a Clinical Associate Professor in the 
Department of Preventive Medicine, School of Medicine 
at the State University of New York at Stony Brook. She 
is a fellow of the American College of Preventive 
Medicine and the New York Academy of Medicine. Her 
career includes work in genetics, solo private practice, 
Grandview Clinic, the Flathead Indian Reservation in 
Poison, Montana, and as volunteer physician for 
CARE-Medico in Bangladesh. 



60 The Tuberculosis Story: From Koch to the Year 2000 



Smallpox and Measles in Mali: 
Contrasting Control Strategies and 
Outcomes 



Pascal James Imperato 



The last naturally transmitted case of hu- 
man smallpox occurred in October 
1977 in Merca, Somalia. In May 1980, the 
Thirty-third World Health Assembly ac- 
cepted the report of the Global Commission 
for the Certification of Smallpox Eradica- 
tion, which affirmed that the disease was 
eradicated. 1 

The intensive worldwide effort to eradi- 
cate smallpox began in 1966 when the Nine- 
teenth World Health Assembly established 
an Intensified Smallpox Eradication Pro- 
gram and provided it with a budget of $2.4 
million. 2 What made the objective of eradi- 
cation possible were several technological 
advances, including automatic jet injectors, 
bifurcated needles capable of swift and safe 
vaccine delivery, and the development of 
heat-stable, freeze-dried smallpox vaccines. 
Equally important was the steady develop- 
ment of a commitment to eradicate small- 
pox. Developing a consensus around that 
objective was greatly facilitated through the 
leadership of the World Health Organiza- 
tion (WHO). 

In the United States, the Centers for Dis- 
ease Control (CDC), an agency of the U.S. 
Public Health Service, developed significant 
expertise in smallpox control during the 




1950s and early 1960s. The name of this 
agency has been changed several times. It 
was originally known as the Communicable 
Disease Center, and later as the National 
Communicable Disease Center, the Center for 
Disease Control, the Centers for Disease Con- 
trol, and finally as the Centers for Disease 



Vie Republic of 
Mali (courtesy 
U.S. Department 
o/State) 



CADUCEUS ♦ Spring 1996 ♦ Vol. 12, No. 1 



Late eruptive 
stage of smallpox 
in a young boy, 
Koutiala, Mali, 
1967 





Control and Prevention. In 1962 the CDC 
established a Smallpox Surveillance Unit 
under the direction of Dr. J. Donald Millar, 
who had had experience with the disease in 
Indonesia. Millar's unit was part of the CDC 
Surveillance Section, then headed by Dr. 
Donald A. Henderson, who would later be- 
come Chief of the WHO Smallpox Eradica- 
tion Unit. 

By early 1965, the CDC had clearly dem- 
onstrated in Brazil that a recently developed 
foot-powered jet injector could rapidly vac- 
cinate large numbers of people against 
smallpox. That important technological ad- 
vance, coupled with the availability of 
freeze-dried vaccines, put eradication 
within reach. Although WHO had a firm 
commitment to smallpox eradication, public 
health officials in West Africa were more 
concerned with measles, which had a higher 



mortality rate than smallpox. There, small- 
pox was a relatively mild disease. 

During 1962 and 1963, Dr. Paul Lambin, 
Minister of Health of Upper Volta (now 
Burkina Faso), and Dr. Harry Meyer of the 
U.S. Division of Biological Standards organ- 
ized the vaccination of some 700,000 chil- 
dren against measles in that country. The 
dramatic decline in measles incidence fol- 
lowing that campaign created a demand by 
other West African countries for similar pro- 
grams. The request found a positive re- 
sponse within the U.S. Agency for 
International Development (USAID), the 
branch of the State Department responsible 
for foreign assistance. To some degree, the 
positive response by USAID was shaped by 
the Cold War political environment, which 
significantly influenced United States for- 
eign assistance programs, especially in 
newly independent African nations. 

Former French colonies in West Africa 
were and still are joined in a regional com- 
municable disease control organization 
known as the Organisation de Coordination 
et de Cooperation pour la Lutte Contre les 
Grandes Endemies (OCCGE). A similar or- 
ganization existed for former French colo- 
nies in Central Africa. Within the context of 
these regional groupings, the governments 
of African countries were able to make a 
concerted appeal for help with measles con- 
trol. 

The CDC interest in smallpox eradication 
and the USAID commitment to help with 
measles control represented potentially di- 
vergent public health objectives. Bringing 
them together in a unified American foreign 
assistance program required much negotiat- 
ing effort on the part of both the CDC and 
USAID as described in great detail by Hor- 



62 Smallpox and Measles in Mali 



ace Ogden. 3 Unifying the programs in the 
field in French-speaking West African coun- 
tries was relatively easy since each had mul- 
tipurpose mobile health teams that were 
part of endemic disease services. 

In late 1966 and early 1967, the CDC and 
USAID jointly set up a smallpox eradica- 
tion/measles control program in nineteen 
West and Central African countries. The 
United States government pledged some $33 
million for the effort. 4 To implement the pro- 
gram, the CDC hired and trained medical 
officers and operations officers, most of 
whom were in place in Africa by early 1967. 

The Republic of Mali 

Mali is a landlocked country in the semi- 
arid interior of West Africa. It covers 478,767 
square miles and shares borders with seven 
countries. Formerly known as the French 
Sudan, Mali became independent in 1960 
under a Marxist government that then main- 
tained close bilateral ties with China, the 
Soviet Union, and the Eastern Bloc. 

At the inception of Mali's smallpox eradi- 
cation/measles control program in late 1966, 
the country had a population of four million. 
Approximately 90 percent lived in rural ar- 
eas as either subsistence farmers or nomadic 
herdsmen. Because of its location, Mali has 
been subjected to cyclical droughts. In most 
years, however, the country is self-sufficient 
in food production. The major exports are 
cattle and hides, fish, and cotton. 

The population of Mali has since more 
than doubled to nine million. The rural 
population of Mali is comprised of several 
different ethnic groups, only some of whom 
share linguistic and cultural characteristics. 
Approximately 65 percent of the population 
is Moslem, and the remainder follow various 
indigenous religions. 5 




Mali's Health Services in the 1960s and 1970s 

Health services in Mali were first estab- 
lished in the 1890s, primarily by French mili- 
tary physicians. As the colonial government 
expanded, these physicians also provided 
services to the indigenous population. It was 
apparent to medical officers that health serv- 
ices had to become mobile and had to stress 
disease prevention if they were to have an 
appreciable impact on the health of the 
population. For that reason, and to deal with 
trypanosomiasis, a mobile medical service 
was established in French West Africa in 
1939. In Mali, the service was called the Serv- 
ice National des Grandes Endemies (En- 
demic Disease Service), which conducted 
mass immunization programs and also pro- 
vided diagnosis and treatment for leprosy, 
trypanosomiasis, malaria, trachoma, tuber- 
culosis, and other communicable diseases. 



Early eruptive 
stage of smallpox 
in a young boy, 
Ansongo, Mali, 



1967 



Pascal James Imperato 63 




Author removing smallpox scabs for laboratory testing, Lellehoi, Mali, 1967. 
The child being held on the left is in the early stage of the disease. 



Health services were quickly Africanized 
in Mali in 1960 at independence, in contrast 
to some neighboring states that maintained 
closer ties with France. During the 1960s, 
large numbers of medical and paramedical 
personnel came from the Soviet Union, 
North Vietnam, and the People's Republic of 
China. Malians were sent to study medicine 
in the Soviet Union, Poland, and the German 
Democratic Republic. Most Malians who 



went to study medicine in France (about one 
hundred persons), however, did not return. 

The colonial government also established 
the Assistance Medicale, the curative-care 
system, which was greatly expanded after 
independence. The medical care infrastruc- 
ture for the 1970s included two national hos- 
pitals (Point-G and Gabriel Toure), a 
regional ophthalmologic hospital adminis- 
tered by the Organisation de Coordination 
et de Cooperation pour la Lutte Contre les 
Grandes Endemies (OCCGE) and nine re- 
gional- and cercle-level (district) hospitals. 
In principle, each of the forty-six cercles and 
281 arrondissements (ward subdivisions) 
was intended to have health centers, al- 
though in 1966 most arrondissements did 
not. In the 1960s and 1970s, more than half 
of the health personnel — as well as most of 
the drugs and supplies — were in the capital, 
Bamako, and served only 8 percent of the 
total national population. The Ministry of 
Health budget then ranged from 4 to 8 per- 
cent of the national budget; most health fa- 
cilities were operated by the government 
and most personnel were government em- 
ployees. In general, facilities were poorly 
maintained, suffered numerous equipment 
breakdowns, and — unless supported by 
outside donor projects — frequently lacked 
basic supplies and medications. Personnel 
costs were met by decreasing funds allo- 
cated for drugs and supplies. Thus, many 
facilities were only marginally functional. 6 

At the inception of the Mali smallpox 
eradication/measles control program in late 
1966, most mobile teams of the Endemic Dis- 
ease Service had not been functioning for a 
few years because of a lack of vehicles, spare 
parts, and funds for fuel. Some of the older 
personnel were extremely experienced in 
the delivery of mobile health services, how- 
ever. In anticipation of the inception of the 



64 Smallpox and Measles in Mali 



USAID program, the government hired a 
score of young men in 1966 to be trained as 
vaccinators. Most were teenagers who had 
been eliminated from continuing their sec- 
ondary education through competitive ex- 
aminations. 

The Smallpox Eradication/Measles 
Control Program in Mali 

The smallpox eradication/measles con- 
trol program for Mali was funded at a level 
of $1.2 million for a five-year period. That 
amount covered twenty Dodge trucks and 
spare parts, equipment, vaccines, and the 
personnel costs of a medical and operations 
officer. Jay Friedman and Mark D. Lapointe 
successively served as operations officers 
between 1966 and 1971. The program was 
administratively linked to the Endemic Dis- 
ease Service. Because that agency was with- 
out a director from 1966 through 1968, the 
USAID personnel related directly to the 
Malian Director General of Health. 

USAID advisors assisted the Malian Min- 
istry of Health in establishing a comprehen- 
sive smallpox eradication/measles control 
program, set targets for it, and helped im- 
prove the disease surveillance system so as 
to permit the early detection of smallpox 
cases. The American advisors also were re- 
sponsible for the training of Malian person- 
nel, which included training in the handling 
of vaccines, use and repair of the Ped-O-Jet 
automatic jet injectors, organization and ad- 
ministration of vaccination sessions, mainte- 
nance and repair of the trucks, disease 
surveillance, and recordkeeping. 

Obstacles to the Success of the Program 

USAID personnel confronted several seri- 
ous problems. The Marxist political climate 
of Mali became increasingly radicalized in 
1967 with the launching of a cultural revolu- 



tion by then-President Modibo Keita. Offi- 
cial anti- American sentiment was extremely 
strong, regularly expressed over the national 
radio and in the government-run newspa- 
per. That sentiment was fueled by the Viet- 
nam War and Mali's strong support of North 
Vietnam. Mali was a highly controlled Marx- 
ist state in which westerners, and especially 
Americans, were viewed with suspicion. 
The active harassment of the American dip- 
lomatic community was encouraged by the 
government. Not surprisingly, the Ameri- 
can staff often found it difficult to secure 
cooperation from Malian health officials. 

A smallpox eradication program had been 
started in Mali in 1962. Using two mobile 
teams and fifteen persons, it administered 
both freeze-dried vaccine produced in the 
Soviet Union and yellow fever vaccine made 
in Senegal. From the outset, the program had 
been handicapped bv the lack of trained per- 
sonnel, vehicles, and fuel. In addition, the 
absence of functioning refrigerators resulted 
in vaccine being stored at high ambient tem- 
peratures. As a result, heat-induced vaccine 
deterioration resulted in low "take" rates 
among those vaccinated. 

Another problem was that people were 
not vaccinated in their villages but called to 
assembly points several miles away. As a 
result, there was selective vaccination of spe- 
cific age groups. Children too big to be car- 
ried and too small to walk were left 
unvaccinated, as were the elderly and those 
occupied with agricultural labor. 

Despite the administration of almost two 
million doses of smallpox vaccine between 
1962 and 1966, cases of smallpox continued 
to occur in Mali. However, the annual num- 
ber of reported cases declined to 281 in 1966. 
A WHO team assessing the Malian program 
in 1965 described the prospects of eradica- 
tion as "bleak." The report estimated that it 



Pascal James Imperato 65 





&#*** 



^ • 



Autlior holding a vaccination session for Pad nomads near Lake Debo in the Inland Delta of the Niger, Mali, 
1968 



would take a decade to eradicate the dis- 
ease. 7 

The American advisors were thus faced 
with a cadre of personnel whose training 
had to include the unlearning of bad habits 
concerning vaccine handling and the use of 
assembly points. 

A WHO smallpox eradication advisor, a 
Czechoslovak national, had been first as- 
signed to Mali in December 1965. The 
American staff developed a generally close 
personal and professional relationship with 
this individual. The Malian Director General 
of Health refused to accept any program 
organization advice from the American per- 
sonnel with which the WHO advisor did not 
concur. When the Americans saw the need 



to personally investigate reported cases of 
smallpox, the WHO advisor preferred to 
leave that task to Malian health personnel in 
the field, and as a result, the Director General 
refused the Americans permission to leave 
the capital. It is likely that even in the ab- 
sence of the WHO advisor, the Director Gen- 
eral would have taken that course of action, 
since the Malian government placed strin- 
gent travel restrictions on Americans. Also, 
the Director General might have feared sig- 
nificant political risks for himself if he had 
given permission to USAID personnel to 
freely travel around the country. Eventually, 
the WHO advisor was withdrawn; the Di- 
rector General of Health left the country to 
become Secretary-General of the OCCGE, 



66 Smallpox and Measles in Mali 



and the Malian government relented on its 
travel restrictions when faced with possible 
program suspension. A Malian physician, 
Ousmane Sow, was then appointed director 
of the Endemic Disease Service, and along 
with the new Director General of Health, 
Daouda Keita, established a close collegial 
relationship with the American team. 8 Both 
doctors had received Masters of Public 
Health degrees from the University of Mont- 
real. 

Smallpox in Mali, 1966-1970 

During the twenty-nine-year period, 
1940-1969, smallpox in Mali was charac- 
terized by epidemic peaks every five to 
seven years. Prior to 1966, the disease was 
endemic in most of the country, with the 
highest incidence rates in the Inland Delta of 
the Niger and in the southern part of the 
country. The former is a vast area of swamps 
and floodplains the size of Maine. It is inhab- 
ited by migrating fisherman and nomadic 
herdsmen. Although the 1962-1965 small- 
pox campaign had numerous deficiencies, it 
resulted in cases falling from 1,706 (1961) to 
284 (1966). 9 

The pre-1967 mass vaccination strategy in 
which assembly points were used and the 
lack of subsequent maintenance programs 
produced specific nonimmune populations, 
including newborns, the elderly, nomads, 
and small children who did not go to assem- 
bly points. 10 

Epidemic investigations in 1967-1969 re- 
vealed that the disease was transmitted 
slowly and primarily in the dry season. The 
latter reflected increased population move- 
ments and human contacts. In closed com- 
munities with high levels of susceptibility, 
smallpox transmission was sustained for 
long periods of time. The overall mortality 
was a low 5.7 percent, and laboratory studies 



from outbreaks confirmed that the virus was 
variola minor. 11 

Measles in Mali, 1966-1970 

The annual number of cases of measles 
reported in Mali in 1966-1970 ranged from 
ten thousand to forty thousand with a mor- 
tality of 15-20 percent. These statistics ex- 
plain why West African health officials were 
far more interested in measles control than 
in smallpox eradication. Measles in Mali was 
primarily a disease of young children, with 
85.4 percent of cases occurring between six 
months and two years of age. 

The severity of measles in Mali and other 
countries in West Africa was in part due to 
such co-morbidities as marginal nutritional 
levels, intercurrent infections, and an un- 
sanitary environment. Traditional beliefs 
and practices also contributed to measles 
morbidity and mortality. For example, chil- 
dren sick with measles were often denied 
protein and hydration out of fear that they 
impeded the emergence of the rash. The 
emergence of the rash was viewed as impor- 
tant as it coincided with a diminution in 
severity of such other symptoms as myalgia, 
coryza, cough, fever, and photophobia. Such 
practices and others made children more 
susceptible to the complications of the dis- 



ease 



12 



Contrasting Perceptions of Smallpox and 
Measles in Mali 

Malian public health officials viewed 
measles as a far more serious problem than 
smallpox. The perception was under- 
standable given the much higher incidence 
of measles and its high mortality rate. Small- 
pox, on the other hand, was viewed as a far 
less serious public health problem. Yet, the 
overriding priori ty of the USAID/CDC small- 
pox eradication/measles control program in 



Pascal James Imperato 67 



the nineteen participating countries of West 
Africa was smallpox eradication. 

Marian health officials tried to structure a 
mass immunization program in response to 
reported measles morbidity. USAID person- 
nel, on the other hand, fostered a strategy 
that gave the priority to smallpox eradica- 
tion. The latter strategy did not lessen overall 
success in controlling measles, given the 
available resources. 

The Beginning of the Mass Immunization 
Campaign 

Six mobile teams of vaccinators and male 
nurses were initially trained by the Ameri- 
can advisors. Eventually, several more 
teams were established and traveled to vil- 
lages and nomad camps in Dodge trucks. 

During the first half of 1967, the central 
region of Bamako was vaccinated. A total of 
384,000 smallpox vaccinations were given, 
and 115,000 children between six months 
and six years were immunized against mea- 
sles. That campaign, launched shortly after 
the arrival of the American advisors, re- 
flected the principal focus of Malian health 
officials on measles control. 13 

While the campaign was under way, the 
American personnel began investigating 
smallpox outbreaks. By the spring of 1967, it 
was clear that most cases were occurring in 
the Inland Delta of the Niger and adjacent 
areas through which nomadic Peul herds- 
men moved with their cattle. That area of 
Mali covered four administrative regions, 
parts of which were inaccessible for several 
months because of seasonal flooding. 

Driven by a desire to control measles, 
Malian health officials next planned to send 
vaccination teams to the western region of 
Kayes. There had been no major smallpox 
outbreaks in that area for a long time, how- 
ever. Given the timing of Mali's rainy season 



(June through September), the Malians 
planned to begin this campaign in October. 

Change to a Strategy of Eliminating Smallpox 
Foci 

Early experiences with investigating 
smallpox epidemics in Mali and success in 
controlling them through intensified sur- 
veillance and vaccination convinced the 
American advisors of the need to change the 
mass campaign strategy. It made no sense to 
them to have mobile teams giving smallpox 
vaccinations in smallpox-free areas of the 
country while outbreaks were occurring 
elsewhere. The American advisors proposed 
that the next dry-season mass vaccination 
campaign be launched in the Mopti region 
and the adjacent districts of the Segou and 
Sikasso regions corresponding to the zone 
where most smallpox cases were occurring. 

Malian health officials were cool to the 
suggestion. The Director General of Health 
repeatedly said, "Measles is knocking on the 
door of the Kayes region." He thus was mak- 
ing a case for a measles-control-driven strat- 
egy. Also, the Kayes region was remote and 
poorly served by public services. Malians 
saw obvious political advantages in a mass 
immunization campaign against measles in 
a region that had received litle from the cen- 
tral government since independence. 14 

The American advisors kept pressing 
their case through the spring of 1967. As part 
of their effort, they invited Dr. George I. 
Lythcott, director of the regional office of the 
CDC West African Smallpox Eradica- 
tion/Measles Control Program, to come 
from Lagos, Nigeria, to Mali. On April 19 he 
and the American advisors set off on an 
extensive ten-day trip through the smallpox 
endemic area of the Inland Delta of the Ni- 
ger. They were accompanied by Dr. Beni- 
tieni Fofana, chief of the Nutrition Division 



68 Smallpox and Measles in Mali 




A Vaccination team poses in Mali, 1967: (standing, left to right) Dr. Jiri Nedvideck (WHO advisor), Zahn 
Sabaker Traore, Sandiougou Dembele, Jean Paul Lastonillas (French cooperation advisor), Aliou Ballo; and 
(kneeling, left to right) Sei/dou Camara, Author, Bama Cisse, and Khalifa Dembele. 



of the Ministry of Health. Fofana (who later 
became Minister of Health) was one of the 
country's leading physicians. His opinions 
were highly respected by the Malian govern- 
ment. The team met with local administra- 
tive and health officials, investigated 
smallpox cases, and spoke with personnel of 
the Veterinary Service who knew the move- 
ments of nomadic groups. 

Malian public health officials, who had 
previously made travel outside the capital 
difficult, readily consented to the trip. Their 
intent was to allow the Americans to see 
first-hand how difficult it would be to 
launch the proposed campaign. They said 
that to chart the movements of the nomads 
and migrating fishermen on the Niger River 
and arrange for the transportation of vacci- 



nators by canoe, camel, and horse would 
require at least a year for planning alone. 

After a grueling trip through the Inland 
Delta of the Niger, the American advisors 
were firmly convinced of the necessity of 
launching a campaign aimed at eliminating 
smallpox foci at the beginning of the next 
dry season in October 1967. The Director 
General of Health resisted, on the grounds 
that such a campaign required much more 
planning time. Conversely, however, he and 
other government officials also saw a year's 
delay as enabling them to deliver measles 
vaccinations to the Kayes region. 

Fofana and Lythcott threw their consider- 
able influence behind the October campaign. 
Eventually, the Director General of Health 
agreed. In October, after several months of 



Pascal James Imperato 69 




-~.- ." 7 



]ay S. Friedman (left) trams vaccinators in the use of the Ped-O-Jet injector, 1967. 



meticulous planning, eight teams of vaccina- 
tors were sent into the Inland Delta of the 
Niger. The teams had to cover 150,000 
square miles of cliffs, sand dunes, plains, 
and swamps; they planned to enter three 
thousand villages and more than one thou- 
sand nomad camps in order to conduct a 
monumental vaccination of a quarter of 
Mali's population: 1,500,000 people against 
smallpox, 300,000 children against measles, 
and 600,000 people against yellow fever. The 
campaign had to be completed within nine 
months, before the June rains. A similar but 
smaller smallpox containment vaccination 



program was conducted in the Gao region in 
the circle of Ansongo. 15 

Development of the E 2 Strategy of Eliminating 
Smallpox Foci 

By June, the eight teams had delivered 
1,425,560 smallpox vaccinations. Surveil- 
lance for smallpox was greatly improved, 
and outbreaks had been investigated and 
contained. Outbreak investigations, in- 
creased surveillance, and targeted vaccina- 
tions resulted in a quick interruption of 
transmission that routine mass immuniza- 
tions could not have achieved. The strategy 



70 Smallpox and Measles in Mali 



of epidemiologic control of smallpox 
launched in Mali in 1967 eliminated the dis- 
ease by 1969. This strategy was successful 
primarily because it was directed at those 
who had the disease and those who were 
most likely to get it. 

As the Malian vaccination campaign was 
ending in June 1968, Dr. J. Donald Millar, the 
director of the CDC smallpox program, in- 
troduced a plan for eradication at a regional 
meeting in Abidjan, Ivory Coast. Developed 
by Dr. William H. Foege, who was then 
working in Nigeria, the plan included active 
surveillance, outbreak investigations, out- 
break control, and rapid communication of 
disease intelligence. 16 

Known as E 2 the plan differed from the 
basic 1967-1968 Malian effort in that it in- 
cluded active surveillance (as opposed to the 
passive receipt of notification) and rapid 
communication of disease intelligence. E 2 
was adopted in late 1968 by Mali and seven 
other West African countries where small- 
pox was still present. 

Outcome of the Smallpox Eradication Program 

By June of 1970, 4,170,608 smallpox vacci- 
nations had been given in the attack phase 
of the program. This represented better than 
90 percent coverage of Mali's estimated 
population. The last case of smallpox was 
detected in 1969. Thus, smallpox was effec- 
tively eliminated from Mali in three years. 

Following the attack phase of the pro- 
gram, maintenance vaccinations were ad- 
ministered to children so as to prevent the 
buildup of a nonimmune population. 

Outcome of the Measles Control Effort 

While public health specialists believed 
that smallpox could be eradicated in Mali, no 
one held the same view with regard to mea- 
sles. The reasons had to do with technologi- 



cal and population concerns. For measles, 
the best hope was control. Although measles 
vaccine could be delivered by automatic jet 
injector, it was much less heat-stable than 
smallpox vaccine. Even minimal levels of 
mishandling in the field and a breakdown in 
cold-chain storage resulted in inactivated 
vaccine. 

Of greater significance were the high 
birthrates in Mali and other West African 
countries that created a fast-growing pool of 
susceptible children. Measles became highly 
endemic and communicable in such a large 
populations of susceptible children. (Small- 
pox, on the other hand, had a lower level of 
endemicity and communicability; it spread 
slowly in Mali, even amid large populations 
of susceptibles.) 

The eradication of measles in Mali and 
Africa in general would have required in- 
tense ongoing immunization programs 
aimed at protecting susceptibles. Outbreak 
investigations, active surveillance, and 
rapid communication of disease intelli- 
gence — as were used in the eradication esca- 
lation program for smallpox — would also 
have been necessary. However, the strategy 
of the smallpox eradication/measles control 
program was largely driven by the desire to 
eradicate smallpox. Measles control was, in 
a sense, grafted onto that objective. 

Contrasting Outcomes 

The two outcomes of the program — small- 
pox eradication and measles control — stand 
in sharp contrast to one another. The rela- 
tively lower level of endemicity and commu- 
nicability of smallpox certainly facilitated 
quick interruption of transmission. Con- 
versely, the high endemicity and communi- 
cability of measles sharply challenged 
efforts to interrupt its transmission. While 
most people immunized against measles in 



Pascal James Imperato 71 



Mali in 1967-1971 were protected against the 
disease, high communicability and the quick 
build-up of large pools of susceptibles be- 
cause of the high birthrates made it impossi- 
ble to eradicate the disease with the 
resources then available. 

Conclusion 

Smallpox was quickly eradicated in Mali 
by 1969 through a strategy of eliminating 
foci of the disease and mass vaccinations. 
The low level of communicability of the dis- 
ease facilitated the success of this strategy. 
Measles, on the other hand, was only con- 
trolled, and then but for a brief period of 
time. The high Malian birthrate quickly es- 
tablished large pools of susceptible children. 
The successful long-term control of measles 
or even its eradication would have required 
much more intensive and ongoing immuni- 
zation programs. These programs would 
have had to regularly reach the vast majority 
of susceptible children. 



Notes 



1. F. Fenner et al., Smallpox and Its Eradication 
(Geneva: World Health Organization, 1988), 1066- 
67, ix. 

2. Ibid., vii. 

3. Horace G. Ogden, CDC and the Smallpox Cru- 
sade (Atlanta: Center for Disease Control, U.S. De- 
partment of Health and Human Services, 1987), 
21-35. 

4. Fenner, Smallpox, 860. 

5. Pascal J. Lmperato, Mali: A Search for Direction 
(Boulder, Colo.: Westview Press, 1989), 1-13. 

6. Ibid., 102-3. 

7. "Smallpox Eradication Programme Report to 
the Director-General," Official Records of the World 
Health Organization 143, Annex 19 (1965): 161-75. 

8. Fenner, Smallpox, 893-94. 

9. "Smallpox Eradication Programme ," 161-75. 
10. Pascal J. lmperato, Ousmane Sow, and Beni- 

tieni Fofana, "The Epidemiology of Smallpox in the 



Republic of Mali," Transactions of the Royal Society of 
Tropical Medicine and Hygiene 66 (1972): 176-82. 

11. Ibid. 

12. D. C. Morley, "Measles and Measles Vaccine 
in Pre- Industrial Countries," Modern Trends in Medi- 
cal Serology, ed R. B. Health and A. P. Waterson 
(London: Butterworths, 1963), 141; Pascal J. lm- 
perato, "Traditional Attitudes towards Measles in 
the Republic of Mali," Transactions of the Royal Society 
of Tropical Medicine and Hygiene 63 (1969): 768-80. 

13. Pascal J. lmperato, A Wind in Africa: A Story of 
Modern Medicine in Mali (St. Louis: Warren H. Green, 
1975), 349. 

14. Personal communication to the author by the 
Director General of Health, Bamako, Mali, 1967. 

15. Pascal J. lmperato, Benitieni Fofana, and Ous- 
mane Sow, "Strategie et tactique pour la vaccination 
des populations du delta interieur du Niger," Afrique 
Medicale 14 (1975): 307-16; Pascal J. lmperato, An 
Outline to the Movements of the Pastoral Peul and the 
Migratory Bozo Fishermen in the Inland Delta of the 
Niger (Atlanta, Ga.: U.S. Department of Health, Edu- 
cation, and Welfare, 1969). 

16. W. H. Foege, J. D. Millar, and J. M. Lane, 
"Selective Epidemiologic Control in Smallpox 
Eradication," American Journal of Epidemiology 94 
(1971): 311-15. 



PASCAL JAMES IMPERATO, M.D., spent five years in 
Mali directing a smallpox eradication and measles 
control program. A specialist in public health and 
tropical medicine, he later served as Commissioner of 
Health of New York City. He is currently Distinguished 
Service Professor and Chair of the Department of 
Preventive Medicine and Community Health at the 
State University of New York, Health Science Center at 
Brooklyn. 



72 Smallpox and Measles in Mali 



X 



BOARD OF ADVISORS 



lames T. H. Connor 
Hannah Institute for the History 
of Medicine 

Glen W. Davidson 
Doane College 

M. Patricia Donahue 
College of Nursing 
University of Iowa 

James Edmonson 

Cleveland Health Sciences Library 

Christopher Hoolihan 
Edward G. Miner Library 
University of Rochester 



Joel Howell 

Clinical Scholars Program 

University of Michigan 

Ramunas Kondratas 
National Museum of American 
History 

Adrianne Noe 

National Museum of Health and 
Medicine 

Gretchen Worden 
Mutter Museum 



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Forthcoming in 
CADUCEUS 

"The Temple of Health: An Illustrated History of the Battle Creek Sanitarium" 

Patsy Gerstner, Guest Editor 

Richly illustrated account of the Michigan institution that was rightly called "one of 
the greatest health experiments of all times." 



Forthcoming Issues 

Howard S. Barrows, Guest Editor, "Medical Education for the Future" 

Eric Curtis, Guest Editor, "History of Dentistry" 

Jonathan Erlen, Guest Editor, "Federal Drug Policy" 

Robert Goler, Guest Editor, "Social Presentations of Anatomy" 

Alan Haiok, Guest Editor, "Medical Spoils of War" 

William G. Rothstein, Guest Editor, "When Did a Random Patient Benefit 

from a Random Physician?" 
Reflate Wilson, Guest Ed/for,"Eighteenth-Cenrury Traffic in Medicines and 

Medical Ideas" 



The Editor also welcomes unsolicited manuscripts. Information on style is given on the 

inside back cover of this issue.